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The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury.
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Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii.
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Sistemas CRISPR-Cas , Factores Eucarióticos de Iniciación , Proteínas Protozoarias , Toxoplasma , Toxoplasma/genética , Toxoplasma/patogenicidad , Toxoplasma/metabolismo , Toxoplasma/crecimiento & desarrollo , Animales , Ratones , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Factores Eucarióticos de Iniciación/genética , Factores Eucarióticos de Iniciación/metabolismo , Virulencia/genética , Toxoplasmosis/parasitología , Toxoplasmosis/genética , HumanosRESUMEN
Establishing an intact intracellular parasitophorous vacuole (PV) that enables efficient nutrient uptake and protein trafficking is essential for the survival and proliferation of Toxoplasma gondii. Although the PV membrane (PVM)-localized dense granule protein 17 (GRA17) and GRA23 mediate the permeability of the PVM to small molecules, including nutrient uptake and excretion of metabolic by-products, the molecular mechanism by which T. gondii acquires nutrients remains unclear. In this study, we showed that the secreted protein GRA47 contributed to normal PV morphology, PVM permeability to small molecules, growth, and virulence in T. gondii. Co-immunoprecipitation analysis demonstrated potential interaction of GRA47 with GRA72, and the loss of GRA72 affected PV morphology, parasite growth and infectivity. To investigate the biological relationship among GRA47, GRA72, GRA17 and GRA23, attempts were made to construct strains with double gene deletion and overexpressing strains. Only Δgra23Δgra72 was successfully constructed. This strain exhibited a significant increase in the proportion of aberrant PVs compared with the Δgra23 strain. Overexpressing one of the three related GRAs partially rescued PVs with aberrant morphology in Δgra47, Δgra72 and Δgra17, while the expression of the Plasmodium falciparum PVM protein PfExp2, an ortholog of GRA17 and GRA23, fully rescued the PV morphological defect in all three Δgra strains. These results suggest that these GRA proteins may not be functionally redundant but rather work in different ways to regulate nutrient acquisition. These findings highlight the versatility of the nutrient uptake mechanisms in T. gondii, which may contribute to the parasite's remarkable ability to grow in different cellular niches in a very broad range of hosts.
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OBJECTIVE: The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner. METHODS: A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy. RESULTS: Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93-1). CONCLUSION: The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment.
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Neoplasias Encefálicas , Progresión de la Enfermedad , Glioma , Imágenes de Resonancia Magnética Multiparamétrica , Recurrencia Local de Neoplasia , Humanos , Glioma/diagnóstico por imagen , Glioma/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Anciano , Máquina de Vectores de Soporte , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Estudios Retrospectivos , RadiómicaRESUMEN
Pathogenicity of the zoonotic pathogen Toxoplasma gondii largely depends on the secretion of effector proteins into the extracellular milieu and host cell cytosol, including the dense granule proteins (GRAs). The protein-encoding gene TGME49_299780 was previously identified as a contributor to parasite fitness. However, its involvement in parasite growth, virulence and infectivity in vitro and in vivo remains unknown. Here, we comprehensively examined the role of this new protein, termed GRA76, in parasite pathogenicity. Subcellular localization revealed high expression of GRA76 in tachyzoites inside the parasitophorous vacuole (PV). However, its expression was significantly decreased in bradyzoites. A CRISPR-Cas9 approach was used to knock out the gra76 gene in the T. gondii type I RH strain and type II Pru strain. The in vitro plaque assays and intracellular replication showed the involvement of GRA76 in replication of RH and Pru strains. Deletion of the gra76 gene significantly decreased parasite virulence, and reduced the brain cyst burden in mice. Using RNA sequencing, we detected a significant increase in the expression of bradyzoite-associated genes such as BAG1 and LDH2 in the PruΔgra76 strain compared with the wild-type Pru strain. Using an in vitro bradyzoite differentiation assay, we showed that loss of GRA76 significantly increased the propensity for parasites to form bradyzoites. Immunization with PruΔgra76 conferred partial protection against acute and chronic infection in mice. These findings show the important role of GRA76 in the pathogenesis of T. gondii and highlight the potential of PruΔgra76 as a candidate for a live-attenuated vaccine.
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Toxoplasma , Animales , Ratones , Toxoplasma/genética , Virulencia/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
Serine/arginine-rich (SR) proteins are key factors with important roles in constitutive and alternative splicing (AS) of pre-mRNAs. However, the role of SR splicing factors in the pathogenicity of T. gondii remains largely unexplored. Here, we investigated the role of splicing factor SR2, a homolog of Plasmodium falciparum SR1, in the pathogenicity of T. gondii. We functionally characterized the predicted SR2 in T. gondii by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The results showed that SR2 was localized in the nucleus and expressed in the tachyzoite and bradyzoite stages. In vitro studies including plaque formation, invasion, intracellular replication, egress and bradyzoite differentiation assays showed that deletion of SR2 in type I RH strain and type II Pru strains had no significant effect on the parasite growth and bradyzoite differentiation (p > 0.05). Interestingly, the disruption of SR2 in RH type I (p < 0.0001) and Pru type II (p < 0.05) strains resulted in varying degrees of attenuated virulence. In addition, disruption of SR2 in type II Pru strain significantly reduced brain cyst burden by ~80% (p < 0.0001). Collectively, these results suggest that splicing factor SR2 is important for the pathogenicity of T. gondii, providing a new target for the control and treatment of toxoplasmosis.
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The Zinc finger protein (ZFP) family is widely distributed in eukaryotes and interacts with DNA, RNA, and various proteins to participate in many molecular processes. In the present study, the biological functions of eight ZFP genes in the lytic cycle and the pathogenicity of Toxoplasma gondii were examined using the CRISPR-Cas9 system. Immunofluorescence showed that four ZFPs (RH248270-HA, RH255310-HA, RH309200-HA, and RH236640-HA) were localized in the cytoplasm, and one ZFP (RH273150-HA) was located in the nucleus, while the expression level of RH285190-HA, RH260870-HA, and RH248450-HA was undetectable. No significant differences were detected between seven RHΔzfp strains (RHΔ285190, RHΔ248270, RHΔ260870, RHΔ255310, RHΔ309200, RHΔ248450, and RHΔ236640) and the wild-type (WT) strain in the T. gondii lytic cycle, including plaque formation, invasion, intracellular replication, and egress, as well as in vitro virulence (p > 0.05). However, the RHΔ273150 strain exhibited significantly lower replication efficiency compared to the other seven RHΔzfp strains and the WT strain, while in vivo virulence in mice was not significantly affected. Comparative expression analysis of the eight zfp genes indicates that certain genes may have essential functions in the sexual reproductive stage of T. gondii. Taken together, these findings expand our current understanding of the roles of ZFPs in T. gondii.
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N6-methyladenosine (m6A) modification is a common epigenetic modification. It is reported that lncRNA can be regulated by m6A modification. Previous studies have shown that lncRNAs associated with m6A regulation (m6A-lncRNAs) serve as ideal prognostic biomarkers. However, whether lncRNAs are involved in m6A modification in colon adenocarcinoma (COAD) needs further exploration. The objective of this study was to construct an m6A-lncRNAs-based signature for patients with COAD. We obtained the RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was employed to recognize lncRNAs associated with m6A regulation (m6A-lncRNAs). 24 prognostic m6A-lncRNAs was identified by univariate Cox regression analysis. Gene set enrichment analysis (GSAE) was used to investigate the potential cellular pathways and biological processes. We have also explored the relationship between immune infiltrate levels and m6A-lncRNAs. Then, a predictive signature based on the expression of 13 m6A-lncRNAs was constructed by the Lasso regression algorithm, including UBA6-AS1, AC139149.1, U91328.1, AC138207.5, AC025171.4, AC008760.1, ITGB1-DT, AP001619.1, AL391422.4, AC104532.2, ZEB1-AS1, AC156455.1, and AC104819.3. ROC curves and K M survival curves have shown that the risk score has a well-predictive ability. We also set up a quantitative nomogram on the basis of risk score and prognosis-related clinical characteristics. In summary, we have identified some m6A-lncRNAs that correlated with prognosis and tumor immune microenvironment in COAD. In addition, a potential alternative signature based on the expression of m6A-lncRNAs was provided for the management of COAD patients.
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The information on Chlamydia infection in cattle is limited in Shanxi Province, north China. This study aimed to investigate the seroprevalence and risk factors of Chlamydia and Chlamydia abortus infection in cattle in Shanxi Province. In November 2020, a large-scale investigation of Chlamydia seroprevalence was conducted on 981 cattle serum samples collected from 40 cattle farms in 11 cities of Shanxi Province. The seroprevalence of Chlamydia and C. abortus was examined by indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA), respectively. The seroprevalence of Chlamydia and C. abortus was 52.29% (513/981) and 2.96% (29/981), respectively, in cattle in Shanxi Province. Location was identified as a risk factor for Chlamydia and C. abortus infection (p < 0.05). Under different management patterns, the seroprevalence of Chlamydia and C. abortus in large-scale animal farming companies was higher than that in household animal farms and animal farming cooperatives, and only the seroprevalence of Chlamydia was significantly different in different management patterns (p < 0.01). The results showed that there was higher seroprevalence of Chlamydia in cattle in Shanxi Province, while C. abortus was not the dominant species. This study provided baseline information on Chlamydia infection in cattle in Shanxi Province, which constitutes valuable data for monitoring livestock health and preventing potential zoonoses.
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A protein of Eimeria tenella (encoded by the locus ETH_00028350) homologous to Toxoplasma gondii dense granule protein 9, designated as EtHGRA9 hereafter, was reported to be expressed in all life cycle stages of E. tenella. However, no data are currently available regarding its functional properties. In the present study, a recombinant vector harboring a 741 bp gene segment encoding the mature form of EtHGRA9 was constructed and transfected into leghorn male hepatoma (LMH) cells. Then, transcriptomic analysis of the transfected LMH cells was carried out by using a high-throughput RNA-seq technology. The LMH cells overexpressing EtHGRA9 was validated by means of Western blotting as well as indirect immunofluorescence staining. The results demonstrated that the expression of 547 genes (275 upregulated genes and 272 downregulated genes) was altered by EtHGRA9. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the ten genes with differential expression between the two groups was consistent with the transcriptome analysis. According to pathway enrichment analysis for the obtained differentially expressed genes, seven pathways were significantly affected by EtHGRA9, such as cytokine-cytokine receptor interaction, MAPK signaling pathway, and protein processing in endoplasmic reticulum. Our data reveal several possible roles of EtHGRA9 in immune or inflammatory responses, which paves the way for a better understanding of the molecular interplay between E. tenella and its host.
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BACKGROUND: Toxocara canis is distributed worldwide, posing a serious threat to both human and dog health; however, the pathogenesis of T. canis infection in dogs remains unclear. In this study, the changes in microRNA (miRNA) expression profiles in the bone marrow of Beagle dogs were investigated by RNA-seq and bioinformatics analysis. RESULTS: Thirty-nine differentially expressed (DE) miRNAs (DEmiRNAs) were identified in this study. Among these, four DEmiRNAs were identified at 24 h post-infection (hpi) and all were up-regulated; eight DEmiRNAs were identified with two up-regulated miRNAs and six down-regulated miRNAs at 96 hpi; 27 DEmiRNAs were identified with 13 up-regulated miRNAs and 14 down-regulated miRNAs at 36 days post-infection (dpi). Among these DEmiRNAs, cfa-miR-193b participates in the immune response by regulating the target gene cd22 at 24 hpi. The novel_328 could participate in the inflammatory and immune responses through regulating the target genes tgfb1 and tespa1, enhancing the immune response of the host and inhibiting the infection of T. canis at 96 hpi. In addition, cfa-miR-331 and novel_129 were associated with immune response and self-protection mechanisms at 36 dpi. 20 pathways were significantly enriched by KEGG pathway analysis, most of which were related to inflammatory response, immune response and cell differentiation, such as Cell adhesion molecules (CAMs), ECM-receptor interaction and Focal adhesion. CONCLUSIONS: These findings suggested that miRNAs of Beagle dog bone marrow play important roles in the pathogenesis of T. canis infection in dogs and provided useful resources to better understand the interaction between T. canis and the hosts.
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MicroARNs , Toxocariasis , Animales , Perros , Médula Ósea/metabolismo , Médula Ósea/parasitología , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , MicroARNs/genética , MicroARNs/metabolismo , Toxocara canis/genética , Toxocariasis/genética , Toxocariasis/metabolismoRESUMEN
The sodium storage mechanism of a GeP5/C composite electrode was revealed. Metallic Ge formed during discharge enhances the electronic conductivity of the electrode, while NaxP mitigates the agglomeration and volume change of Ge in the alloying process. The GeP5 phase is regenerated after recharge along with elemental Ge and P, implying a reversible phase transition of GeP5 during cycling.
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Objective: The present study aims to explore the effects of different numbers of fiberoptic bronchoscopic examinations on the nosocomial infection/colonization of carbapenem-resistant Enterobacteriaceae (CRE). Methods: The data of 129 patients admitted to the intensive care unit of a grade 3A hospital were retrospectively analyzed, and CRE nosocomial infection/colonization situations in patients with fiberoptic bronchoscope application times of 1, 2, 3, and ≥4 were statistically analyzed. Results: The incidence of nosocomial infection/colonization of CRE increased significantly when the number of fiberoptic bronchoscopic examinations was ≥3. Conclusion: Nosocomial infection/colonization of CRE is highly correlated with an increased number of fiberoptic bronchoscopic examinations.
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BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.
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Objective: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method: Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children's leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result: The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan-Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion: The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.
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BACKGROUND: To evaluate the antidepressant effects of auricular intradermal acupuncture (AIA) of areas innervated by both the auricular branch of the vagus nerve and the trigeminal nerve. METHODS: Forty-nine patients with depression were randomly allocated into an AIA group (n = 25) and a sham AIA group (n = 24). Both groups received selective serotonin reuptake inhibitors (SSRIs) as conventional treatment. The AIA group received AIA stimulation, and the sham AIA group received sham AIA, which constituted being subjected to an attached needle that did not penetrate the skin. The needles were retained for 4 h each session, with five sessions a week for a total duration of 2 weeks. The outcomes were assessed by the 17-item Hamilton depression rating scale (HAMD-17), five factors (sleep disorder, retardation, cognitive dysfunction, anxiety/somatization, and weight) and self-rating depression scale (SDS) at weeks 0, 1, and 2. RESULTS: Fifty-four patients were randomly assigned to the AIA (n = 27) and sham AIA group (n = 27), of whom 25 patients in the AIA and 24 patients in the sham AIA group were analyzed. AIA-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores (p = 0.03) and SDS scores (p = 0.02) at week 2 compared to patients receiving sham AIA. The AIA intervention also produced a higher rate of clinically significant responses in sleep disorders (p = 0.07) compared to sham AIA. No adverse events occurred in either group. CONCLUSION: According to the findings of this preliminary study, AIA appears to have additional value compared to SSRIs alone in treating patients with depressive disorder.
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Acupuntura Auricular , Depresión/terapia , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto , Terapia Combinada , Depresión/tratamiento farmacológico , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Oxygen-redox of layer-structured metal-oxide cathodes has drawn great attention as an effective approach to break through the bottleneck of their capacity limit. However, reversible oxygen-redox can only be obtained in the high-voltage region (usually over 3.5 V) in current metal-oxide cathodes. Here, we realize reversible oxygen-redox in a wide voltage range of 1.5-4.5 V in a P2-layered Na0.7 Mg0.2 [Fe0.2 Mn0.6 â¡0.2 ]O2 cathode material, where intrinsic vacancies are located in transition-metal (TM) sites and Mg-ions are located in Na sites. Mg-ions in the Na layer serve as "pillars" to stabilize the layered structure during electrochemical cycling, especially in the high-voltage region. Intrinsic vacancies in the TM layer create the local configurations of "â¡-O-â¡", "Na-O-â¡" and "Mg-O-â¡" to trigger oxygen-redox in the whole voltage range of charge-discharge. Time-resolved techniques demonstrate that the P2 phase is well maintained in a wide potential window range of 1.5-4.5 V even at 10 C. It is revealed that charge compensation from Mn- and O-ions contributes to the whole voltage range of 1.5-4.5 V, while the redox of Fe-ions only contributes to the high-voltage region of 3.0-4.5 V. The orphaned electrons in the nonbonding 2p orbitals of O that point toward TM-vacancy sites are responsible for reversible oxygen-redox, and Mg-ions in Na sites suppress oxygen release effectively.
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BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.