ABO and Rhesus blood groups and multiple health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.

Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis.

BACKGROUND: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. METHODS: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). RESULTS: Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. CONCLUSION: Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.

Physicochemical, structural and functional properties of low methoxyl pectin­iron (III) complex and its effect on rats with iron deficiency anemia.

Iron deficiency anemia (IDA) is the most common nutritional disease worldwide. In this study, a low methoxyl pectin (LMP)­iron(III) complex was prepared. The physicochemical and structural properties were characterized by HPSEC, HPIC, CV, FTIR, 1H NMR, XRD, SEM and CD. The results showed that iron increased the molecular weight of the LMP­iron(III) from 11.50 ± 0.32 to 12.70 ± 0.45 kDa and improved its crystallinity. Moreover, the findings demonstrated that -OH and -COOH groups in LMP coordinate with Fe3+ to form ß-FeOOH. The water-holding capacity, emulsion stability, and antioxidant activities of the LMP­iron(III) were lower than those of LMP. Furthermore, the therapeutic effects of LMP­iron(III) on IDA were investigated in rats. Following LMP­iron(III) supplementation, compared with the model group, the administration of LMP­iron(III) significantly increased the body weight, hemoglobin concentration, and serum iron concentration as well as decreased free erythrocyte protoporphyrin concentration. Therefore, the LMP­iron(III) can potentially treat IDA in rats experiments, providing a theoretical basis for the development of a promising iron supplement.

Nuclear KRT19 is a transcriptional corepressor promoting histone deacetylation and liver tumorigenesis.

BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice. Cell fractionation revealed a previously unrecognized nuclear fraction of KRT19. Tandem affinity purification identified histone deacetylase 1 and REST corepressor 1, components of the corepressor of RE-1 silencing transcription factor (CoREST) complex as KRT19-interacting proteins. KRT19 knockout markedly enhanced histone acetylation levels. Mechanistically, KRT19 promotes CoREST complex formation by enhancing histone deacetylase 1 and REST corepressor 1 interaction, thus increasing the deacetylase activity. ChIP-seq revealed hepatocyte-specific genes, such as hepatocyte nuclear factor 4 alpha ( HNF4A ), as direct targets of KRT19-CoREST. In addition, we identified forkhead box P4 as a direct activator of aberrant KRT19 expression in liver cancer. Furthermore, treatment of primary liver tumors and patient-derived xenografts in mice suggest that KRT19 expression has the potential to predict response to histone deacetylase 1 inhibitors especially in combination with lenvatinib. CONCLUSIONS: Our data show that nuclear KRT19 acts as a transcriptional corepressor through promoting the deacetylase activity of the CoREST complex, resulting in dedifferentiation of liver cancer. These findings reveal a previously unrecognized function of KRT19 in directly shaping the epigenetic landscape in cancer.

Risk factors for post-operative portal vein stenosis in pediatric liver transplantation: a single center case-control study.

PURPOSE: The incidence of post-transplant poral vein stenosis (PVS) is higher in pediatric liver transplantation, probably resulting from various portal vein (PV) reconstruction methods or other factors. METHODS: 332 patients less than 12 years old when receiving liver transplantation (LT) were enrolled in this research. Portal vein reconstruction methods include anastomosis to the left side of the recipient PV trunk (type 1, n = 170), to the recipient left and right PV branch patch (type 2, n = 79), using vein graft interposition (type 3, n = 32), or end-to-end PV anastomosis (type 4, n = 50). The incidence of PVS was analyzed in terms to different PV reconstruction methods and other possible risk factors. RESULTS: PVS occurred in 35 (10.5%) patients. Of the 32 patients using vein graft, 20 patients received a cryopreserved vein graft, 11 (55%) developed PVS, while the remaining 12 patients received a fresh iliac vein for PV interposition and none of them developed PVS. 9 patients whose liver donor was under 12 years old developed PVS, with an incidence of 18.8%. CONCLUSION: Cryopreserved vein graft interposition and a liver donor under 12 are independent risk factors for PVS in pediatric LT.

Universal antifungal prophylaxis effectively prevents fungal bloodstream infection in pediatric liver transplant recipients: a retrospective real-world study.

OBJECTIVES: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. METHODS: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. RESULTS: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). CONCLUSIONS: Universal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.

PBX3 as a biomarker for the early diagnosis and prediction of prognosis of glioma.

BACKGROUND: Increasing evidence have elucidated that PBX3 played a crucial role in cancer initiation and progression. PBX3 was differentially expressed in many cancer types. However, PBX3 potential involvement in gliomas remains to be explored. METHODS: The expression level of PBX3 in glioma tissues and glioma cells, and its correlation with clinical features were analyzed by data from TCGA, GEPIA, CGGA and CCLE. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival. We also analyzed the correlation between PBX3 expression level and survival outcome and survival time of LGG and GBM patients by using linear regression equation. GSEA was used to generate an ordered list of all genes related to PBX3 expression and screening of genes co-expressed with PBX3 mRNA by "limma" package. RESULTS: The results showed that PBX3 was highly expressed in gliomas and its expression increased with the increase of malignancy. Survival analysis found that PBX3 is more valuable in predicting the OS and PFI of LGG patients than that of GBM. For further study, TCGA and CGGA data were downloaded for univariate Cox analysis and multivariate Cox analysis which showed that the expression of PBX3 was independent influencing factors for poor prognosis of LGG patients. Meanwhile, Receiver operating characteristic (ROC) curve showed that PBX3 was a predictor of overall survival rate and progression-free survival rate of LGG. Linear regression model analysis indicated that the higher expression of PBX3 the higher the risk of death of LGG patients, and the higher expression of PBX3 the higher the risk of disease progression of LGG patients. Next, TCGA data were downloaded for GSEA and Co-expression analyses, which was performed to study the function of PBX3. CONCLUSION: PBX3 may be involved in the occurrence and development of glioma, and has potential reference value for the early diagnosis and prediction of prognosis of glioma.

Position Prior Attention Network for Pancreas Tumor Segmentation.

Segmentation of pancreatic tumors on CT images is essential for the diagnosis and treatment of pancreatic cancer. However, low contrast between the pancreas and the tumor, as well as variable tumor shape and position, makes segmentation challenging. To solve the problem, we propose a Position Prior Attention Network (PPANet) with a pseudo segmentation generation module (PSGM) and a position prior attention module (PPAM). PSGM and PPAM maps pancreatic and tumor pseudo segmentation to latent space to generate position prior attention map and supervises location classification. The proposed method is evaluated on pancreatic patient data collected from local hospital and the experimental results demonstrate that our method can significantly improve the tumor segmentation results by introducing the position information in the training phase.

Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders.

Lysosomal storage disorders (LSDs), which are characterized by genetic and metabolic lysosomal dysfunctions, constitute over 60 degenerative diseases with considerable health and economic burdens. However, the mechanisms driving the progressive death of functional cells due to lysosomal defects remain incompletely understood, and broad-spectrum therapeutics against LSDs are lacking. Here, we found that various gene abnormalities that cause LSDs, including Hexb, Gla, Npc1, Ctsd and Gba, all shared mutual properties to robustly autoactivate neuron-intrinsic cGAS-STING signalling, driving neuronal death and disease progression. This signalling was triggered by excessive cytoplasmic congregation of the dsDNA and DNA sensor cGAS in neurons. Genetic ablation of cGAS or STING, digestion of neuronal cytosolic dsDNA by DNase, and repair of neuronal lysosomal dysfunction alleviated symptoms of Sandhoff disease, Fabry disease and Niemann-Pick disease, with substantially reduced neuronal loss. We therefore identify a ubiquitous mechanism mediating the pathogenesis of a variety of LSDs, unveil an inherent connection between lysosomal defects and innate immunity, and suggest a uniform strategy for curing LSDs.

Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance.

Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer.Abbreviation: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.

18F-FAPI-04 Outperforms 18F-FDG PET/CT in Clinical Assessments of Patients with Pancreatic Adenocarcinoma.

Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized by hypometabolism. Here, we investigated 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18F-FDG. Methods: Sixty-two PDAC patients underwent 18F-FAPI-04 PET/CT and 18F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUVmax of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18F-FAPI-04 PET/CT identified all patients with PDAC; 18F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18F-FAPI-04 PET/CT than in 18F-FDG PET/CT in primary tumors (10.63 vs. 2.87, P < 0.0001), LN metastasis (2.90 vs. 1.43, P < 0.0001), and DM (liver, 6.11 vs. 3.10, P = 0.002; peritoneal, 4.70 vs. 2.08, P = 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for 18F-FAPI-04 PET/CT than for 18F-FDG PET/CT (P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18F-FAPI-04 PET/CT compared with 18F-FDG PET/CT. A high SUVmax of the primary tumor did not correlate with treatment response for either 18F-FAPI-04 or 18F-FDG. Conclusion: 18F-FAPI-04 PET/CT performed better than 18F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.

Hurdle or thruster: Glucose metabolism of T cells in anti-tumour immunity.

Glucose metabolism is essential for the activation, differentiation and function of T cells and proper glucose metabolism is required to maintain effective T cell immunity. Dysregulation of glucose metabolism is a hallmark of cancer, and the tumour microenvironment (TME2) can create metabolic barriers in T cells that inhibit their anti-tumour immune function. Targeting glucose metabolism is a promising approach to improve the capacity of T cells in the TME. The efficacy of common immunotherapies, such as immune checkpoint inhibitors (ICIs3) and adoptive cell transfer (ACT4), can be limited by T-cell function, and the treatment itself can affect T-cell metabolism. Therefore, understanding the relationship between immunotherapy and T cell glucose metabolism helps to achieve more effective anti-tumour therapy. In this review, we provide an overview of T cell glucose metabolism and how T cell metabolic reprogramming in the TME regulates anti-tumour responses, briefly describe the metabolic patterns of T cells during ICI and ACT therapies, which suggest possible synergistic strategies.

Clinical characteristics and outcomes of liver transplant recipients infected by Omicron during the opening up of the dynamic zero-coronavirus disease policy in China: A prospective, observational study.

We analyzed the characteristics, risk factors, outcomes, and post-coronavirus disease 2019 (COVID-19) symptoms in liver transplant recipients in China's late 2022 COVID-19 wave. Recipients with COVID-19 were enrolled from December 1, 2022, to January 31, 2023, and followed up until May 31, 2023. Baseline and characteristic data were collected. A total of 930 recipients were included, with a vaccination rate (non-mRNA) of 40.0%. Among 726 (78.1%) recipients with COVID-19, 641 (88.3%) patients were treated at home, 81 (11.2%) patients required hospitalization in general wards, 4 (0.6%) patients required intensive care, and 1 (0.1%) patient died because of COVID-19. Severe acute respiratory syndrome coronavirus 2 infection was related to close contact with confirmed cases (P < .001) and the condition of end-stage kidney disease (P < .046). Older age, male sex, less vaccination, and hypertension were independent risk factors for hospitalization. Fatigue (36.9%) was the most common symptom post-COVID-19, followed by memory loss (35.7%) and sleep disturbance (23.9%). Two doses of vaccines had a protective effect against these post-COVID-19 symptoms (P < .05). During this Omicron outbreak, liver transplant recipients were susceptible to COVID-19, with frequent hospitalization but low mortality. Two doses of non-mRNA COVID-19 vaccines could protect against liver transplant recipient hospitalization and post-COVID-19 symptoms.

Siamese Delta Network with Multimodality Fusion for Systemic Treatment Response Prediction in Pancreatic Cancer.

Systemic treatment is a main way for pancreas cancer patients that are ineligible for surgery. A subgroup of patients showed good response to systemic treatment and the rest received limited benefits. CT images provide a non-invasive way to assess the treatment response. Alternative non-image methods include radiology analysis, tumor marker analysis and combination analysis. To combine the image and non-image data, we propose the Siamese Delta Network with Multimodality Fusion (SDN-MF) to predict systemic treatment response in an end-to-end way. First, a Siamese Delta Network (SDN) is designed to process pre-treatment and pre-surgery CT images and get the image feature changes to predict response. Then, patients' characteristics from EMR and alternative analysis results forms non-image data, which is incorporated into SDN with a multimodality fusion (MF) module. The proposed SDN-MF is evaluated on a private dataset and achieves average AUC value of 0.883 with five cross-validation. Comparison among image-only, non-image-only, and fusion models verifies the superior of multimodality model in predicting systemic treatment response of pancreas cancer patients.

In vitro and in vivo killing effects of methionine enkephalin on osteosarcoma.

OBJECTIVE: This study aimed to investigate the underlying regulatory effects of methionine enkephalin (MENK) on osteosarcoma. METHODS: The Cell Counting Kit-8 assay, clone formation, wound healing, transwell assay, and flow cytometry were performed to measure the effects of MENK on the proliferation, migration, invasion, and apoptosis of MG-63 and Saos-2 cells. Opiate growth factor receptor expression (OGFr) in cells was stably knocked down using siRNA. A tumor model was established by inoculating MG-63 cells into mice. Flow cytometry was performed to identify alterations in mice bone marrow, spleen, and tumor tissue immune cells. The phenotype of tumor-associated macrophages was determined using immunohistochemistry. After OGFr knockdown or/and treatment with MENK, Bax, Bcl-2, caspase 3, caspase 9, and PARP expression levels were characterized using qRT-PCR, western blot, and WES, respectively. RESULTS: MENK could significantly inhibit the proliferation, invasion, and migration of MG-63 and Saos-2, arrest the cell cycle in the G0/G1 phase, upregulate Bax, caspase 3, caspase 9, and PARP expression, and downregulate Bcl-2 expression. Tumor size and weight were lower in the MENK group than those in the control group. MENK-treated mice exhibited a reduced ratio of CD11b + Gr-1 + myeloid-derived suppressor cells. MENK increased the ratio of M1-type macrophages and decreased the proportion of M2-type macrophages in tumor tissue. Furthermore, the level of TNF-α significantly increased while that of IL-10 decreased in MENK-treated mice. The effect of MENK could be partly reversed by OGFr knockdown. CONCLUSION: MENK reduces the abundance of myeloid-derived suppressor cells, induces M1 polarization of macrophages, and exhibits an inhibitory effect on osteosarcoma.

Improve the prediction of liver transplant mortality based on pre-transplant factors: A multi-center study from China: Mortality prediction of LT.

AIMS: To designed a new model using pre-transplant data to predict post-transplant mortality for Chinese population and compared its performance to that of existing models. METHODS: In this multicenter study, 544 recipients of liver transplants for non-tumor indications were enrolled in the training group and 276 patients in the validation group. The new Simplified Mortality Prediction Scores (SMOPS) model was compared to the MELD and four existing models using the C-statistic. RESULTS: SMOPS model used 6 independent pre-transplantation risk factors screened from the training group (chronic liver failure/organ failure scores, fever > 37.6 â„ƒ, ABO blood-type compatibility, arterial lactate level, leukocyte count and re-transplantation). The SMOPS accurately predicted patients' 30-day, 90-day and 365-day mortality following liver transplantation, and its' scores were more accurate than those of the other models. The SMOPS generated four levels of risk: low risk (<10 points), moderate risk (11-20 points), high risk (21-25 points) and futile risk (≥26 points). The survival within all risk levels was not different between MELD=40 and MELD<40. The survival within moderate-, high- or extreme-risk ALF was not different between ALF and non-ALF. CONCLUSION: The SMOPS model uses pre-transplant risk factors to stratify post-transplant survival and is superior to current models for Chinese population, and has the potential to contribute to improvements in organ-allocation policies.