To elucidate the diagnostic value and clinical relevance of protein kinase D3 (PRKD3) in hepatocellular carcinoma (HCC), we analyzed data retrieved from The Cancer Genome Atlas (TCGA) database, which revealed high expression of PRKD3 in HCC tissues. Subsequently, we collected a total of 392 clinical plasma samples from healthy individuals, patients with cirrhosis or decompensated cirrhosis, and patients with HCC. Plasma PRKD3 levels were then determined across HCC patients and individuals at high risk of developing the disease. The results revealed significantly elevated PRKD3 concentrations in patients with cirrhosis, decompensated cirrhosis, and HCC compared to healthy controls (P<0.01). The areas under the receiver operating characteristic (ROC) curve for these three groups were 0.8107, 0.7899, and 0.7177, respectively. To further evaluate the efficacy of PRKD3 as an adjunctive diagnostic biomarker for HCC, we employed a panel of machine learning algorithms as primary classifiers, including extra trees (ET), gradient boosting (GB), random forest (RF), and support vector machine (SVM). A multiparameter joint diagnostic model was constructed by combining PRKD3 expression data with a set of clinical parameters, including gender, age, total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence-II (PIVKA-II). This integrated approach exhibited substantially improved diagnostic performance, achieving an accuracy of 0.861, sensitivity of 0.863, specificity of 0.925, and precision of 0.862. Collectively, these findings highlight the potential of PRKD3 as an integral component of a comprehensive diagnostic tool for the early identification of HCC.

BackgroundAs a major global health concern, liver injury requires effective preventive and therapeutic measures. This study aimed to examine the relationship between eosinophil and basophil counts and liver injury.MethodsWe analyzed two cohorts: 16, 328 subjects from a hospital-based dataset and 14, 962 individuals from the NHANES (2007-2012) database. After excluding cases with missing values, participants were categorized into groups with or without liver injury. Statistical analyses included weighted logistic regression (across three models), the XGBoost algorithm to identify critical factors, and restricted cubic spline analysis to explore non-linear relationships.ResultsStatistical analyses revealed significant differences in eosinophil and basophil counts in peripheral blood between the liver injury and non-injury groups. Weighted logistic regression demonstrated a significant association between these cell counts and liver injury across all three models, independent of other covariates. The XGBoost algorithm identified eosinophil and basophil counts as critical factors for liver injury, ranking second and third in importance after age. Restricted cubic spline analysis showed a non-linear relationship between eosinophil count and the odds ratio (OR), with an optimal count of 0.2×109 cells/L. Furthermore, higher eosinophil and basophil counts were correlated with reduced overall survival (OS) in patients with liver injury.ConclusionThese findings highlight eosinophil and basophil counts as potential risk factors for liver injury, providing valuable insights for its prevention and treatment.

TLR2 bridges innate and adaptive immunity, with agonists showing promise in vaccines and cancer therapy. In this study, we found natural product CaLGL-1, which functions as a "quiescent agonist" of TLR2, with its immunostimulatory potential masked by a labile acetal group. In an oxidative environment, CaLGL-1 is converted into potent TLR2 agonist. Inspired by this phenomenon, we rationally designed BXY-14, a derivative exhibiting cross-species TLR2 agonist activity. This compound demonstrates exceptional potency (THP-1 cells, EC50 = 2.2 nM; mBMDCs, EC50 = 1.8 nM), and functions as a superior vaccine adjuvant, eliciting stronger antibody responses than Diprovocim. Additionally, in murine models, BXY-14 markedly downregulated intratumoral PD-L1 expression and demonstrated synergistic efficacy with the anti-PD-L1 monoclonal antibody atezolizumab, resulting in significantly prolonged overall survival. Together, this work establishes metabolically gated immunity and delivers a translational TLR2 agonist bridging bacterial metabolite chemistry with immunotherapy.

Breast cancer (BC) poses a persistent global health challenge, necessitating new therapeutic targets. The oncogenic translation factor Eukaryotic translation initiation factor 5A (eIF5A), while implicated in other cancers, lacks a mechanistic definition in BC. In this study, we found that eIF5A was significantly overexpressed in BC and correlated with poor clinical outcomes. Knocking down of eIF5A could suppress BC cell proliferation and migration in vitro, induce apoptosis and cell cycle arrest, and inhibit tumor growth in vivo in the MMTV-PyMT model. Mechanistically, eIF5A depletion induced mitochondrial dysfunction, characterized by elevated reactive oxygen species (ROS), reduced mitochondrial membrane potential (Delta Psi m), compromised ATP synthesis and enhanced oxidative damage. These defects, along with the impaired tumorigenicity, were rescued by overexpressing the mitochondrial protease ATP-dependent Clp protease proteolytic subunit (ClpP). We further demonstrated that eIF5A promoted tumor progression, at least in part, by binding to and enhancing the translation of ClpP mRNA, leading to upregulation of ClpP. Importantly, we identified the eIF5A-ClpP axis as a key regulator of mitochondrial redox homeostasis in BC, and its disruption effectively suppressed malignant phenotypes. These findings established the eIF5A-ClpP axis as a mechanistically grounded and therapeutically targetable vulnerability for BC intervention.

Ubiquitin D, a ubiquitin-like protein, functions as a potential tumor promoter in various cancers. However, its biological role and clinical significance in breast cancer remain unclear. In this study, we evaluated UBD expression in malignant and normal breast tissues using bioinformatics databases. Analysis of clinical specimens showed that UBD expression was significantly higher in primary breast cancer tissues than in normal breast tissues and was closely associated with key clinicopathological features in affected patients. Subsequently, breast cancer cell line models were established to assess the impact of UBD on malignant properties in vitro. KEGG pathway analysis indicated that differentially expressed genes were significantly enriched in the PI3K/AKT signaling pathway. Western blot analysis was performed to examine changes in EMT-related markers and key signaling molecules involved in the PI3K/AKT pathway in breast cancer cells. The PI3K/AKT agonist 740Y-P and inhibitor LY294002 were employed to determine the contribution of this pathway to EMT regulation in breast cancer cells. The results demonstrated that EMT signature-derived ssGSEA scores indicated UBD had the strongest positive correlation with the EMT process, and that UBD enhanced the expression of EMT-related markers in breast cancer cells. The pathway inhibitor LY294002 suppressed UBD-induced increases in migration and invasion, as well as the expression of EMT-related markers. In contrast, the agonist 740Y-P restored the decreased migration, invasion, and EMT phenotypes induced by UBD knockdown. Collectively, our data demonstrated that UBD plays a critical role in the malignant progression of breast cancer, highlighting its potential as a novel therapeutic target for breast cancer patients.

Purpose This study aimed to elucidate the common pathogenic pathways underlying the comorbidity of metabolic-associated fatty liver disease (MASLD) and type 2 diabetes mellitus (T2DM), with particular focus on identifying how gut microbiota and their metabolites regulate host gene expression in these mutually reinforcing metabolic disorders. Methods We employed an integrated multi-omics approach combining Mendelian randomization (MR) analysis with transcriptomic data from GEO datasets (GSE89632 and GSE26168) and gut microbiome GWAS data from MiBioGen. Differential gene expression analysis was performed to identify co-differentially expressed genes. MR analysis screened for disease-associated gut bacteria. Integration of host gene, metabolite, and microbiome data with databases such as gutMGene was conducted to determine key indicators. Functional enrichment analysis, protein-protein interaction network construction, and molecular docking simulations were performed. A predictive linear model was developed and validated using Hosmer-Lemeshow tests and decision curve analysis. Immunohistochemical analysis assessed correlations with immune cell infiltration, and ceRNA regulatory networks were constructed. Results The analysis identified 246 co-differentially expressed genes and 14 key gut bacteria potentially associated with both diseases. Seven key indicators were ultimately determined through data integration. These genes were enriched in lipid metabolism, inflammatory regulation, and redox processes. Four key protein nodes (PTGS2, ALOX15B, KLK3, and DHFR) were identified. Molecular docking revealed strong binding stability between core metabolites (genistein, phenylacetic acid, and N-acetylornithine) and target proteins. The predictive model demonstrated excellent performance with AUC values of 0.982 and 0.903 in the two datasets. Strong correlations were observed between key genes and immune cell infiltration rates, and multi-level ceRNA regulatory mechanisms were uncovered. Conclusion This study demonstrates that the gut microbiota-metabolite-host gene axis plays a critical role in MASLD and T2DM comorbidity. The identified biomarkers and therapeutic targets provide important foundations for accurate prevention, diagnosis, and treatment strategies for these metabolic diseases.

BACKGROUND:Accumulating evidence demonstrates that miRNAs exhibit enhanced diagnostic sensitivity and specificity compared to the conventional hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP), particularly showing promising clinical utility in early-stage HCC detection. However, insufficient transparency in methodology reporting compromises the validity assessment of these findings and hinders their translational applications. In this study, we investigated the adherence to the STARD criteria in studies investigating the diagnostic accuracy of miRNA for liver cancer. In addition, the quality of reporting was examined to identify factors influencing the quality of reporting. METHOD:A comprehensive search strategy was performed on the PubMed, EMBASE, Cochrane Library, and Web of Science, as of March 30, 2023. Clinical trials investigating the diagnostic value of miRNA for HCC diagnosis were included in the analysis. The eligible studies were checked against adherence to the STARD criteria. Factors determining quality of studies were evaluated through subgroup analyses. All statistical analyses were performed using SPSS (varsion25.0). RESULTS:Sixty-two eligible studies, all published between 2010 and 2022, were eventually included in the final analysis. The results revealed a moderate overall adherence to STARD 2015, with an average of 12.1 (52.6%) of the 23 items reported. Subgroup analysis revealed that adherence to the STARD 2015 varied among countries (USA 58.7%;Egypt 46.5%)(p<0.05). CONCLUSION:The quality of studies reporting the diagnostic accuracy of miRNAs in HCC was average and did not increase after the publication of STARD 2015. Our findings rise awareness regarding the need to improve STARD standards, implying that more journals need to include STARD standards for relevant manuscripts. In addition, editorial and peer approval procedures should adopt measures that will aim to improve reporting quality.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with a dismal prognosis. This study established and validated a prognostic model based on antigen-processing and presenting machinery (APM)-related genes through Mendelian randomization and publicly available datasets. Systematic analysis revealed CXCL5, SGPP2, and GLP1R as critical prognostic biomarkers, which were subsequently integrated into a risk model. The model demonstrated significant associations with pathways linked to bile acid, fatty acid, and amino acid metabolism, alongside variations in immune cell infiltration and genomic mutations, including TTN, TP53, and MUC16. Patient stratification into high- and low-risk groups indicated that low-risk individuals exhibited reduced immune infiltration, potentially correlating with enhanced immunotherapy sensitivity. These findings offer a robust gene signature for HCC prognosis and a framework for evaluating responses to immunotherapy.

Protein kinase D3 (PRKD3), belonging to the protein kinase D family, significantly influences tumor development and progression. The role of PRKD3 in advancing gastric cancer (GC) and its effects on the cell cycle are not well understood, necessitating detailed investigation. Assessment of PRKD3 expression in both malignant and normal gastric tissues was performed using bioinformatics databases. The influence of PRKD3 on GC’s malignant characteristics was evaluated through in vitro experiments utilizing cell line models of GC. Additionally, proteomic analyses were conducted to investigate the potential mechanisms of PRKD3 in GC progression. PRKD3 was notably overexpressed in GC tissues, correlating with adverse outcomes for patients. PRKD3 knockdown impaired GC cell malignancy, manifesting as a 2.12-fold decline in proliferation(p < 0.01), 2.64-fold suppression of migration(p < 0.01), 2.16-fold inhibition of invasion(p < 0.01), and G2/M phase arrest. Proteomic and Western blot analyses had revealed a substantial enrichment in differentially expressed proteins (DEPs) associated with tumor-related signaling pathways, including FoxO and p53, which was paralleled by significant alterations in the levels of key cell cycle proteins such as CDK1, CyclinB1, CHK1 and PLK1, with a 6.8-fold elevation in CHK1 levels(p < 0.05). The overexpression of PRKD3 was intricately linked with the aggressive behaviors of GC. Targeting PRKD3 activity offers potential for effective treatments of GC.

Background Circulating tumor DNA (ctDNA) in peripheral blood has become a promising noninvasive biomarker. However, the diagnostic potential of Wnt/beta-catenin signaling pathway-related ctDNA for liver cancer is controversial. Here, we aimed to access the diagnostic potential and clinicopathological features of Wnt/beta-catenin signaling pathway-related ctDNA in liver cancer and provide data support for its clinical diagnosis and treatment. Methods A comprehensive literature search was conducted to identify the relevant studies. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. The bivariate linear mixed models were used. Results The AUC (area under the curve), pooled sensitivity and specificity were 0.77, 0.42 and 0.98, respectively. The findings suggested that control type, sample source, research methods and thresholds were the potential sources of heterogeneity (p < 0.05). Additionally, this study also found that there were significant correlations between the hypermethylation of Wnt/beta-catenin signaling pathway-related ctDNA and tumor size, TNM stage, distant metastasis, and HBV infection(p < 0.05). Conclusion This study confirmed that Wnt/beta-catenin signaling pathway-related ctDNA had the better diagnostic potential for liver cancer and might be an effective complementary tool for serum AFP assays in the early diagnosis of liver cancer. [GRAPHICS] .

BACKGROUND:Protein kinase D 3 (PRKD3), a serine/threonine protein kinase, functions as a crucial regulator across numerous cancer types. However, its regulatory function and mechanism in hepatocellular carcinoma (HCC) proliferation remain unclear. In vitro experiments and proteomics analysis offer new insights into the regulation and mechanism of PRKD3 in HCC. METHODS:A PRKD3 knockdown cell line was constructed to assess the effects of PRKD3 on proliferation of HCC cells using cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, clonogenic assay, and flow cytometry. Proteomic changes in liver cancer cells before and after PRKD3 knockdown were analyzed using 4D-lablefree technology. RESULTS:Analysis of The Cancer Genome Atlas (TCGA) dataset revealed abnormal PRKD3 expression in HCC, associated with poorer prognosis and specific pathological types. Results from the CCK-8 assay showed a marked reduction in the proliferation of Huh7 cells (P < 0.01), with the number of clonal colonies being 5.26 times higher than that in PRKD3 knockdown cells, and the EdU positivity rate decreased from 54.77% to 37.97%. Flow cytometry results indicated that PRKD3 knockout induced cell cycle arrest at G2/M phase. Proteomic analysis revealed 330 proteins had altered expression, associated with amino acid transport, stress response, and apoptosis. Cyclin-dependent kinase 4 (CDK4), plasminogen activator inhibitor 1 (SERPINE1), sequestosome 1 (SQSTM1), ras-related protein Rab-8A (RAB8A), and nuclear receptor-binding factor 2 (NRBF2) emerged as key nodes in the protein interaction network. CONCLUSION:This study elucidates the inhibitory effect of PRKD3 knockdown on HCC proliferation and unveils the proteomic features of PRKD3 regulation. CDK4, SERPINE1, SQSTM1, RAB8A, and NRBF2 may serve as key proteins in PRKD3's regulatory pathways.

Background Several studies have demonstrated that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-related circular RNAs (circRNAs) play a role in the development and progression of hepatocellular carcinoma (HCC). However, a systematic review and meta-analysis of the role of PI3K/AKT-related circRNAs in the diagnosis and prognosis of HCC has not been reported at present. Herein, we systematically reviewed the literature and conducted a meta-analysis of the potential role of PI3K/AKT/mTOR-related circRNAs in the diagnosis and prognosis of HCC. Method PubMed, EMBASE, Cochrane Library, Web of Science, Scoups, Wanfang, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI) and Chinese Science and Technique Journals Database (VIP) databases were searched for relevant studies from inception to April 19, 2024. Pooled odds ratio (OR) was used to evaluate clinical case characteristics, sensitivity and specificity. Prognostic overall survival (OS) was estimated using the hazard ratio (HR). Subgroup analyses were conducted according to sample type, country and control group type. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool or the Newcastle-Ottawa Scale (NOS) method, and Egger’s tests were used to assess potential publication bias. STATA (version 17.0) software was used for statistical analysis. Results Twenty five eligible articles, including ten diagnostic studies and sixteen prognostic studies, involving 2995 HCC patients, 435 healthy controls and 338 controls with benign lesions were included in this meta-analysis. The pooled sensitivity and specificity were 0.80 (95% CI: 0.75–0.84) and 0.86 (95% CI: 0.77–0.92), respectively. Higher levels of PI3K/AKT/mTOR pathway-associated circRNAs are significantly associated with poor patient prognosis (OS:HR = 1.49, 95% Cl: 0.89–2.48, P < 0.001). Elevated levels of highly expressed circRNAs in patients were significantly associated with HbsAg positivity, MVI positivity, and worse TMN staging in patients with HCC, and elevated levels of low expressed circRNAs in patients were associated with MVI negativity in patients with HCC. No publication bias was found. Conclusion PI3K/AKT/mTOR-related circRNAs are potential biomarkers for HCC, especially in the diagnosis of HCC. Due to the small number of included articles and the limitation of the included population, more studies on the diagnostic and prognostic value of PI3K/AKT/mTOR pathway-related circRNAs are needed in the future.

基于党中央出台的加强大学生思想政治工作的文件及使各类课程与思想政治教育同向同行的教育理念,全面构建"大思政"的"检验医学"全新教学模式在高校教学中备受重视.从思政视角及思想政治教育的必要性出发对"检验医学"的传统教学方式、教学环节及教学理念进行更新、改进,并对其进行深入探讨,通过对学生的问卷调查结果进行分析,得出思想政治教育不仅有助于学生提升课程兴趣、更好地掌握专业知识,还有助于进一步全面提升学生的综合素质,为"检验医学"课程的思想政治教学改革提供了参考.

BackgroundPrimary liver cancer is a malignant tumour of the digestive system, ranking second in cancer mortality in China. In different types of cancer, such as liver cancer, microRNAs (miRNAs) have been shown to be dysregulated. However, little is known about the role of miR-5195-3p in insulin-resistant liver cancer.Methods and resultsIn this study, in vitro and in vivo experiments were conducted to identify the altered biological behaviour of insulin-resistant hepatoma cells (HepG2/IR), and we proved that HepG2/IR cells had stronger malignant biological behaviour. Functional experiments showed that enhanced expression of miR-5195-3p could inhibit the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance of HepG2/IR cells, while impaired expression of miR-5195-3p in HepG2 cells resulted in the opposite effects. Bioinformatics prediction and dual luciferase reporter gene assays proved that SOX9 and TPM4 were the target genes of miR-5195-3p in hepatoma cells.ConclusionsIn conclusion, our study demonstrated that miR-5195-3p plays a critical role in insulin-resistant hepatoma cells and might be a potential therapeutic target for liver cancer.

The interruption of normal cell cycle execution acts as an important part to the development of leukemia. It was reported that microRNAs (miRNAs) were closely related to tumorigenesis and progression, and their aberrant expression had been demonstrated to play a crucial role in numerous types of cancer. Our previous study showed that miR-1246 was preferentially overexpressed in chemo-resistant leukemia cell lines, and participated in process of cell cycle progression and multidrug resistant regulation. However, the underlying mechanism remains unclear. In present study, bioinformatics prediction and dual luciferase reporter assay indicated that CADM1 was a direct target of miR-1246. Evidently decreased expression of CADM1 was observed in relapsed primary leukemia patients and chemo-resistant cell lines. Our results furtherly proved that inhibition of miR-1246 could significantly enhance drug sensitivity to Adriamycin (ADM), induce cell cycle arrest at G0/G1 phase, promote cell apoptosis, and relieve its suppression on CADM1 in K562/ADM and HL-60/RS cells. Interference with CADM1 could reduce the increased drug sensitivity induced by miR-1246 inhibition, and notably restore drug resistance by promoting cell cycle progression and cell survival via regulating CDKs/Cyclins complexes in chemo-resistant leukemia cells. Above all, our results demonstrated that CADM1 attenuated the role of miR-1246 in promoting cell cycle progression and cell survival, thus influencing multidrug resistance within chemo-resistant leukemia cells via CDKs/Cyclins. Higher expression of miR-1246 and lower expression of CADM1 might be risk factors for leukemia.

INTRODUCTION This study is to detect the expression of inflammatory factor or neutrophil-activating factor IL-8 and Wnt2 in gastric cancer (GC) and investigate the involvement of IL-8 and Wnt2 expressions in the clinicopathological indexes and prognosis. MATERIAL AND METHODS We detected the expression of IL-8 and Wnt2 in 100 GC tissues and 40 normal gastric mucosae using immunohistochemistry. The relationships between the IL-8 and Wnt2 expression and the clinicopathological characteristics were explored. The relationship between IL-8 expression, Wnt2 expression, and prognosis of GC was analyzed by survival curve and survival regression. RESULTS The expression of IL-8 and Wnt2 in GC tissue was 64% and 75% respectively, which was significantly higher than that in adjacent normal gastric mucosa tissues, moreover, expressions of IL-8 and Wnt2 were positively correlated. The positive rate of IL-8 and Wnt2 expressions were correlated with lymph node metastasis and TNM staging （P < 0.01, and Wnt2 was also correlated with infiltration depth (P = 0.021), but there was no difference with age, sex, and differentiation (P > 0.05). The 3-year survival analysis showed that the survival rates of IL-8- and Wnt2-positive patients were 20% and 24%, respectively, which were significantly lower than those of negative patients. Cox regression analysis showed that IL-8 and Wnt2 may be independent factors affecting the prognosis of GC. CONCLUSIONS Our data demonstrated that the overexpression of IL-8 and Wnt2 could be isolated prognostic factors in patients with GC and, possibly, may present new targets for the treatment of GC.

Objective:To analyze and summarize the overall results of application and funded projects by the National Natural Science Foundation of China (NSFC) in the field of laboratory medicine from 2010 to 2021.Methods:Application and granting data in the field of laboratory medicine during 2010 and 2021 were collected from NSFC. Amount of funded projects, geographical distribution, supporting institution, distribution of keywords and representative research results in the field of laboratory medicine were analyzed. The overall characteristics of funded project in the past decades were summarized.Results:From 2010 to 2021, NSFC received a total of 7 746 project applications, among which 1 152 projects and a total of 506.317 million RMB were funded in the field of laboratory medicine. Project applications increased from 228 in 2010 to 1 184 in 2021. Among them, the number of funded projects increased from 36 in 2010 to 137 in 2021, accompanied by an increase in the amount of project grants from 10.12 million RMB in 2010 to 65.38 million RMB in 2021, but there is still a gap compared with other disciplines. In the field of laboratory medicine (H26), the sub-disciplines H2605 (molecular biological examination) and H2606 (new technologies and methods for laboratory medicine research) were the two directions with the highest number of funded grants, with a total of 688 grants, accounting for 59.7% (688/1 152) of the total funded grants. Among the region of funding, Beijing, Guangdong, Shanghai, Chongqing, Zhejiang and Jiangsu were the top six regions with the successful funding, accounting for 60.2% (695/1 152) funded projects. Thirty supporting institutions received 826 grants in the field of laboratory medicine, accounting for 71.7% (826/1 152) funded projects. Among all the funded projects tumors (37.1%, 427/1 152), infectious diseases (26.9%, 310/1 152), circulatory diseases (5.3%, 61/1 152), autoimmune diseases (4.3%, 49/1 152), and endocrine and metabolic diseases (2.8%, 32/1 152) ranked the top disease types of successful funding; proteins (33.4%, 385/1 152), DNA (19.4%, 224/1 152), RNA (17.3%, 199/1 152), exosomes (6.0%, 69/1 152), and cells (5.9%, 68/1 152) ranked the top targets of successful funding; nanotechnology (6.0%, 69/1 152), mass spectrometry (3.0%, 34/1 152), probe technology (1.82%, 21/1 152), electrochemical technology (1.6%, 19/1 152), and second-generation sequencing technology (1.6%, 18/1 152) ranked the top technologies of funded projects. Within the last decade, many breakthroughs have been made by many distinguished national research groups in developing reference ranges, identifying novel biomarkers, and inventing novel laboratory medicine technologies.Conclusions:The number of projects and the total funding amount are increasing annually in the past decade in the field of laboratory medicine granted by NSFC. The funding of different secondary codes, regions and supporting units varies remarkably, and the scope of funded projects is wide. Many research groups have achieved landmark progress in novel biomarker identification and technology development. The overall level of research in the laboratory medicine is expected to be significantly improved in the future.

Recently, the incidences of insulin resistance (IR) and IR-related complications have increased throughout the world, which also associate with poor prognosis in hepatocellular carcinoma (HCC). Numerous studies had been focused on the role of IR in tumorigenesis and prognosis of HCC. The proteomic analysis of IR related hepatocellular carcinoma had not been reported by now. In the present study, 196 differentially expressed proteins (DEPs) were identified between insulin resistant HepG2 cells and their parental cells, of which 109 proteins were downregulated and 87 proteins were upregulated. Bioinformatics analysis indicated that these DEPs were highly enriched in process of tumorigenesis and tumor progression. PPI network analysis showed that SOX9, YAP1 and GSK3β as the key nodes, were involved in Wnt and Hippo signaling pathways. Survival analysis revealed that high expression of SOX9 and PRKD3 were strongly associated with reduced patient survival rate. parallel reaction monitoring (PRM) and Western blot analysis were applied to verify the protein level of these four key nodes mentioned above, which showed the same trend as quantified by isobaric tags for relative and absolute quantitation (iTRAQ) and confirmed the reliability of our Proteome Profiling analysis. Our results indicated that IR related dysregulation of protein expression might participated in tumorigenesis and malignant phenotype of hepatocarcinoma cells.

A meta-analysis was conducted to evaluate the effectiveness of crucial biomarkers in HepG2 cells during epithelial-mesenchymal transformation induced by multiple interventions. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan Fang Data and VIP databases were systematically searched from inception to June 14, 2020, by two independent reviewers. Results: A total of 58 studies were included in the meta-analysis. E-cadherin, N-cadherin and vimentin performed well undermedicinal interventions. E-cadherinworked well under genetic interventions. E-cadherin and N-cadherin also performed significantly well under tumor microenvironment interventions. Under ncRNA interventions, the expression of E-cadherin significantly changed. Conclusion: Different sets of biomarkers should be selected under various interventions based on their performance.

目的 研究肝母细胞瘤(hepatoblastoma,HB)的发病机制,并为其提供防治的相关生物信息学依据.方法 采用GEO2R在线分析工具分析HB基因芯片GSE131329的HB组织与正常组织,得到差异表达基因(differentially expressed genes,DEGs),并通过R语言制作火山图.DAVID数据库分析DEGs的GO功能与KEGG通路富集分析,STRING数据库与Cytoscape软件绘制蛋白质相互作用(protein-protein interaction,PPI)网络图,筛选关键基因(hub基因)并分析得出功能模块图.GEPIA数据库验证hub基因在HB中的表达量.最后通过CCLE数据库和TIMER数据库分别分析靶基因在HB中的表达情况以及靶基因与炎症细胞浸润的关系.结果 共筛选出266个DEGs,涉及通路主要包括药物代谢、补体激活、细胞周期及癌症相关信号通路.Cytoscape筛选出的hub基因经GEPIA数据库验证,共有6个与临床不良预后相关,其中3个低表达和2个高表达基因差异有统计学意义.靶基因周期蛋白依赖性激酶1(cyclin-dependent kinase 1,CDK1)经CCLE数据库再次证实,在HB组织中高表达.TIMER数据库显示,CDK1与HB炎症细胞浸润相关.结论 CDK1可能通过调节炎症浸润与细胞周期而参与HB的发生发展,这为HB的防治提供了生物信息学依据.