Osimertinib treatment response in a patient with lung adenocarcinoma harboring two rare EGFR mutations: A case report.

Epidermal growth factor receptor (EGFR) mutations have emerged as the most well-studied oncogenic alterations in advanced non-small cell lung cancer. The presence of single common or rare EGFR mutations and extra complex EGFR mutations correlates with the response sensitivity to EGFR tyrosine kinase inhibitors. Therefore, given the lack of evidence for the emergence of rare EGFR mutation types, the pathogenic mechanisms of uncommon EGFR mutations and the optimal treatment strategies remain to be explored further. The present study describes the case of a patient diagnosed with lung adenocarcinoma (LUAD) carrying two rare EGFR exon 18 indel/G719C and exon 19 L747S mutations, in which persistent lesion shrinkage was exhibited within 16 months of osimertinib treatment. Given the paucity of clinical trials for the treatment of LUAD harboring complex EGER mutations, the present detailed case description may provide clinicians with effective clinical experience in treating patients.

Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.

BACKGROUND: Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. METHODS: Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. RESULTS: TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. CONCLUSIONS: Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.

Tumor immune microenvironment of NSCLC with EGFR exon 20 insertions may predict efficacy of first-line ICI-combined regimen.

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.

KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1.

Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.

BRG1 promotes liver cancer cell proliferation and metastasis by enhancing mitochondrial function and ATP5A1 synthesis through TOMM40.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide. Brahma-related gene 1 (BRG1), as a catalytic ATPase, is a major regulator of gene expression and is known to mutate and overexpress in HCC. The purpose of this study was to investigate the mechanism of action of BRG1 in HCC cells. In our study, BRG1 was silenced or overexpressed in human HCC cell lines. Transwell and wound healing assays were used to analyze cell invasiveness and migration. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) detection were used to evaluate mitochondrial function in HCC cells. Colony formation and cell apoptosis assays were used to evaluate the effect of BRG1/TOMM40/ATP5A1 on HCC cell proliferation and apoptosis/death. Immunocytochemistry (ICC), immunofluorescence (IF) staining and western blot analysis were used to determine the effect of BRG1 on TOMM40, ATP5A1 pathway in HCC cells. As a result, knockdown of BRG1 significantly inhibited cell proliferation and invasion, promoted apoptosis in HCC cells, whereas BRG1 overexpression reversed the above effects. Overexpression of BRG1 can up-regulate MMP level, inhibit mPTP opening and activate TOMM40, ATP5A1 expression. Our results suggest that BRG1, as an oncogene, promotes HCC progression by regulating TOMM40 affecting mitochondrial function and ATP5A1 synthesis. Targeting BRG1 may represent a new and effective way to prevent HCC development.

Treatment of late left bronchopleural fistula after left pneumonectomy through right thoracic approach assisted by extracorporeal membrane oxygenation.

BACKGROUND: Bronchopleural fistula (BPF) is a rare but fatal complication after pneumonectomy. When a BPF occurs late (weeks to years postoperatively), direct resealing of the bronchial stump through the primary thoracic approach is challenging due to the risks of fibrothorax and injury to the pulmonary artery stump, and the surgical outcome is generally poor. Here, we report a case of late left BPF following left pneumonectomy successfully treated using a right thoracic approach assisted by extracorporeal membrane oxygenation (ECMO). CASE PRESENTATION: We report the case of a 57-year-old male patient who underwent left lower and left upper lobectomy, respectively, for heterochronic double primary lung cancer. A left BPF was diagnosed at the 22nd month postoperatively, and conservative treatment was ineffective. Finally, the left BPF was cured by minimally invasive BPF closure surgery via the right thoracic approach with the support of veno-venous extracorporeal membrane oxygenation (VV-ECMO). CONCLUSIONS: Advanced BPF following left pneumonectomy can be achieved with an individualized treatment plan, and the right thoracic approach assisted by ECMO is a relatively simple and effective method, which could be considered as an additional treatment option for similar patients.

Bi Nanospheres Embedded in N-Doped Carbon Nanowires Facilitate Ultrafast and Ultrastable Sodium Storage.

Sodium ion batteries (SIBs) are considered as the ideal candidates for the next generation of electrochemical energy storage devices. The major challenges of anode lie in poor cycling stability and the sluggish kinetics attributed to the inherent large Na+ size. In this work, Bi nanosphere encapsulated in N-doped carbon nanowires (Bi@N-C) is assembled by facile electrospinning and carbonization. N-doped carbon mitigates the structure stress/strain during alloying/dealloying, optimizes the ionic/electronic diffusion, and provides fast electron transfer and structural stability. Due to the excellent structure, Bi@N-C shows excellent Na storage performance in SIBs in terms of good cycling stability and rate capacity in half cells and full cells. The fundamental mechanism of the outstanding electrochemical performance of Bi@N-C has been demonstrated through synchrotron in-situ XRD, atomic force microscopy, ex-situ scanning electron microscopy (SEM) and density functional theory (DFT) calculation. Importantly, a deeper understanding of the underlying reasons of the performance improvement is elucidated, which is vital for providing the theoretical basis for application of SIBs.

The Burden of Hypertension-Related Chronic Kidney Disease - China, 2010-2019.

What is already known about this topic?: The global burden of chronic kidney disease (CKD) is on the rise. What is added by this report?: In 2019, 5.58 million individuals in China were affected by CKD related to hypertension, leading to 70,260 fatalities and 1.69 million disability-adjusted life years (DALYs). The most affected groups were men, older individuals, and residents of western China. Over the period from 2010-2019, the age-standardized prevalence rate (ASPR) remained constant, and the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) showed a decreasing trend. However, there was an increase in the number of cases, deaths, and DALYs associated with this condition. What are the implications for public health practice?: Hypertension significantly contributes to the burden of CKD; therefore, raising awareness and implementing early screening measures are essential.

Economic Evaluation of COVID-19 Immunization Strategies: A Systematic Review and Narrative Synthesis.

OBJECTIVES: This study aimed to systematically assess global economic evaluation studies on COVID-19 vaccination, offer valuable insights for future economic evaluations, and assist policymakers in making evidence-based decisions regarding the implementation of COVID-19 vaccination. METHODS: Searches were performed from January 2020 to September 2023 across seven English databases (PubMed, Web of Science, MEDLINE, EBSCO, KCL-Korean Journal Dataset, SciELO Citation Index, and Derwent Innovations Index) and three Chinese databases (Wanfang Data, China Science and Technology Journal, and CNKI). Rigorous inclusion and exclusion criteria were applied. Data were extracted from eligible studies using a standardized data collection form, with the reporting quality of these studies assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). RESULTS: Of the 40 studies included in the final review, the overall reporting quality was good, evidenced by a mean score of 22.6 (ranging from 10.5 to 28). Given the significant heterogeneity in fundamental aspects among the studies reviewed, a narrative synthesis was conducted. Most of these studies adopted a health system or societal perspective. They predominantly utilized a composite model, merging dynamic and static methods, within short to medium-term time horizons to simulate various vaccination strategies. The research strategies varied among studies, investigating different doses, dosages, brands, mechanisms, efficacies, vaccination coverage rates, deployment speeds, and priority target groups. Three pivotal parameters notably influenced the evaluation results: the vaccine's effectiveness, its cost, and the basic reproductive number (R0). Despite variations in model structures, baseline parameters, and assumptions utilized, all studies identified a general trend that COVID-19 vaccination is cost-effective compared to no vaccination or intervention. CONCLUSIONS: The current review confirmed that COVID-19 vaccination is a cost-effective alternative in preventing and controlling COVID-19. In addition, it highlights the profound impact of variables such as dose size, target population, vaccine efficacy, speed of vaccination, and diversity of vaccine brands and mechanisms on cost effectiveness, and also proposes practical and effective strategies for improving COVID-19 vaccination campaigns from the perspective of economic evaluation.

SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects the liver and poses a significant threat to human health. Further investigation is necessary to fully understand the role of SIRT1, a protein linked to tumorigenesis, in HCC development. To investigate the effect of SIRT1 on HCC and elucidate the underlying mechanism. Eight pairs of HCC and paracancerous normal tissue specimens were collected. The levels of SIRT1 and GSDME in tissue samples were assessed using immunohistochemistry and western blotting. SIRT1 levels were determined in HCC (Huh7, HepG2, SNU-423, SNU-398, and HCCLM3) and L-02 cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. SNU-423 and HCCLM3 cells were transfected with si-SIRT1 and/or si-GSDME to knock down SIRT1 or GSDME expression. RT-qPCR and western blotting were performed to measure the expression of SIRT1, pro-casp-3, cl-casp-3, GSDME, GSDME-N, PGC-1α, Bax, and cytochrome c (Cyto C). Cell proliferation, migration, invasion, and apoptosis were assessed using the cell counting kit-8 (CCK-8), wound healing assay, Transwell invasion assay, and flow cytometry, respectively. The release of lactate dehydrogenase (LDH) was evaluated using an LDH kit. SIRT1 was upregulated in HCC tissues and cells, and a negative correlation was observed between SIRT1 and GSDME-N. SIRT1 silencing suppressed the proliferation, migration, and invasion of HCC cells while also promoting apoptosis and inducing mitochondrial damage. Additionally, the silencing of SIRT1 resulted in the formation of large bubbles on the plasma membrane of HCC cells, leading to cellular swelling and aggravated GSDME-dependent pyroptosis, resulting in an increase in LDH release. Inhibition of GSDME reduced SIRT1 silencing-induced cell swelling, decreased LDH release rate, and promoted apoptosis. SIRT1 silencing promotes GSDME-dependent pyroptosis in HCC cells by damaging mitochondria.

Identification of a Novel CD8+ T cell exhaustion-related gene signature for predicting survival in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway.

OBJECTIVE: To investigate the effect of COVID-19 infection on pancreatic cancer. METHODS: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software. RESULTS: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. CONCLUSION: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Site-selective chemical reactions by on-water surface sequential assembly.

Controlling site-selectivity and reactivity in chemical reactions continues to be a key challenge in modern synthetic chemistry. Here, we demonstrate the discovery of site-selective chemical reactions on the water surface via a sequential assembly approach. A negatively charged surfactant monolayer on the water surface guides the electrostatically driven, epitaxial, and aligned assembly of reagent amino-substituted porphyrin molecules, resulting in a well-defined J-aggregated structure. This constrained geometry of the porphyrin molecules prompts the subsequent directional alignment of the perylenetetracarboxylic dianhydride reagent, enabling the selective formation of a one-sided imide bond between porphyrin and reagent. Surface-specific in-situ spectroscopies reveal the underlying mechanism of the dynamic interface that promotes multilayer growth of the site-selective imide product. The site-selective reaction on the water surface is further demonstrated by three reversible and irreversible chemical reactions, such as imide-, imine-, and 1, 3-diazole (imidazole)- bonds involving porphyrin molecules. This unique sequential assembly approach enables site-selective chemical reactions that can bring on-water surface synthesis to the forefront of modern organic chemistry.

Budesonide/formoterol maintenance and reliever therapy in childhood asthma: Real-world effectiveness and economic assessment.

INTRODUCTION: The study aims to compare the real-world effectiveness and economy of the budesonide/formoterol reliever and maintenance therapy (SMART) with fixed-dose inhaled corticosteroids (ICS)/long-acting b-agonist (LABA) or ICS alone plus as-needed, short-acting ß2 agonists (SABA) in pediatric patients. METHODS: The outpatient data warehouse of a hospital in China was used. A total of 103 patients under 18 years old in the SMART group and 63 patients in the control group were included from January 1, 2020 to December 31, 2021. The effectiveness was assessed using asthma attacks and lung function at baseline, 6 months and 12 months follow-up. Cost-effectiveness analysis was performed with a three-state Markov model from the healthcare system perspective. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to check the robustness of the results. RESULTS: The SMART regimen was more effective than other strategies in reducing the risk of mild and severe attacks in the real-life management of childhood asthma. Patients in both groups showed significant improvement in lung function at 6 and 12 months in contrast to baseline. Compared with other strategies, the forced expiratory volume in 1 s (FEV1 ) level in the SMART group was markedly improved at 6 months. The total cost of outpatient service using the SMART regimen was lower than that of other strategies, while the drug costs were similar in different groups. Incremental cost-effectiveness analysis results showed that using the SMART regimen reduced the total cost by approximately CNY 10,516.11 per year with a 0.12 quality-adjusted life year (QALYs) increase. Sensitive analyses supported that the SMART regimen was the dominant choice at the willingness-to-pay threshold of CNY 85,698, per capita GDP in China. CONCLUSIONS: Collectively, our findings indicate that the real-world effectiveness and economy of the SMART regimen are superior to the traditional strategies in pediatric asthma patients.

Effects of dietary sodium butyrate on growth performance, immune function, and intestinal microflora of Chinese soft-shelled turtle (Pelodiscus sinensis).

The Chinese soft-shelled turtle (Pelodiscus sinensis) has become increasingly susceptible to frequent diseases with the intensification of farming, which severely impacts the development of the aquaculture industry. Sodium butyrate (SB) is widely used as a feed additive due to its promotion of growth, enhancement of immune function, and antioxidative properties. This study aimed to investigate the effects of dietary SB on the growth performance, immune function, and intestinal microflora of Chinese soft-shelled turtles. A total of 300 Chinese soft-shelled turtles (mean weight: 11.36 ± 0.21g) were randomly divided into four groups with three parallel sets in each group. Each group was fed a diet supplemented with 0%, 0.005%, 0.01%, or 0.02% SB for 60 days. The results demonstrated an upward trend in weight gain rate (WGR) and specific growth rate (SGR) with increasing SB supplementation, and the experimental group fed with 0.02% SB showed a significant increase in WGR and SGR compared to other groups (P< 0.05). These levels of SB also decreased the levels of feed conversion ratio (FCR) and the total cholesterol (TC) content of Chinese soft-shelled turtles, and the 0.02% SB was significantly lower than that of other groups (P< 0.05). The activity of complement protein in vivo increased with increases in SB content, and the activities of complement C3 and C4 reached the highest level with 0.02% SB. The species abundance of the experimental group D fed with 0.02% SB was significantly higher than that of other groups (P< 0.05). Furthermore, the relative abundance of Clostridium sensu stricto 1 was significantly increased with 0.02% SB (P< 0.05). In conclusion, adding 0.02% SB to the diet improves the growth performance, feed digestion ability, and intestinal microbiota of Chinese soft-shelled turtles.

A Quasi-2D Polypyrrole Film with Band-Like Transport Behavior and High Charge-Carrier Mobility.

Quasi-2D (q2D) conjugated polymers (CPs) are polymers that consist of linear CP chains assembled through non-covalent interactions to form a layered structure. In this work, the synthesis of a novel crystalline q2D polypyrrole (q2DPPy) film at the air/H2 SO4 (95%) interface is reported. The unique interfacial environment facilitates chain extension, prevents disorder, and results in a crystalline, layered assembly of protonated quinoidal chains with a fully extended conformation in its crystalline domains. This unique structure features highly delocalized π-electron systems within the extended chains, which is responsible for the low effective mass and narrow electronic bandgap. Thus, the temperature-dependent charge-transport properties of q2DPPy are investigated using the van der Pauw (vdP) method and terahertz time-domain spectroscopy (THz-TDS). The vdP method reveals that the q2DPPy film exhibits a semiconducting behavior with a thermally activated hopping mechanism in long-range transport between the electrodes. Conversely, THz-TDS reveals a band-like transport, indicating intrinsic charge transport up to a record short-range high THz mobility of ≈107.1 cm2 V-1 s-1 .

Histone demethylases in the regulation of immunity and inflammation.

Pathogens or danger signals trigger the immune response. Moderate immune response activation removes pathogens and avoids excessive inflammation and tissue damage. Histone demethylases (KDMs) regulate gene expression and play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal expression of KDMs is closely associated with the pathogenesis of various inflammatory diseases such as liver fibrosis, lung injury, and autoimmune diseases. Despite becoming exciting targets for diagnosing and treating these diseases, the role of these enzymes in the regulation of immune and inflammatory response is still unclear. Here, we review the underlying mechanisms through which KDMs regulate immune-related pathways and inflammatory responses. In addition, we also discuss the future applications of KDMs inhibitors in immune and inflammatory diseases.

Fabrication of gelatin methacryloyl/graphene oxide conductive hydrogel for bone repair.

The ideal bone repair materials possess a series of properties, such as injectability, good mechanical properties and bone inducibility. In the present study, gelatin methacryloyl (GelMA) and graphene oxide (GO) were selected to prepare conductive hydrogel by changing the concentration of GelMA and GO during the cross-link process. The effects of different contents of GelMA and GO to the hydrogel performance were investigated. The results showed that the mechanical properties of the hydrogel kept 16.37 ± 1.89 KPa after adding 0.1% GO, while the conductivity was improved to 1.36 ± 0.09 µS/cm. The porosity of hydrogel before and after mineralization could reach more than 90%. The mechanical properties of mineralized hydrogel was improved significantly, could reach 26.38 ± 2.29 KPa. Cell experiments indicated that the mineralized hydrogel with electrical stimulation obviously improve the alkaline phosphatase activity of the cells. GelMA/GO conductive hydrogel could be a promising candidate for bone repair and bone tissue engineering.

Risk prediction for dermatomyositis-associated hepatocellular carcinoma.

OBJECTIVE: To explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. METHODS: Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. RESULTS: The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. CONCLUSION: LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.

Diagnosis of gastric cancer based on hybrid genes selection approach.

Gastric cancer (GC) is the third leading cause of cancer death worldwide. In the field of medicine, machine learning is widely used in genetic data mining and the construction of diagnostic models. This study proposed an intelligent model DERFS-XGBoost for rapid and accurate diagnosis of GC based on gene expression data. Firstly, the data of GC were collected and preprocessed. Secondly, ANOVA, t-test and fold chang (FC) were used to select genes that had significant differentially expressed genes (DEGs), and random forest (RF) was used to calculate their importance, and then sequential forward selection (SFS) was used to obtain the optimal feature subset. Finally, XGBoost was used for classification after synthetic minority oversampling technique (SMOTE) balanced between tumor and normal samples. In order to objectively evaluate the results, the 10-fold cross-validation and 10 repeated experiments were used in the experiment, and the average value of the evaluation indexes was used to evaluate the classification effect. Based on the experiment, DERFS-XGBoost model accuracy rate was 97.6%, precision was 100%, the recall rate was 97.3%, F1 was 99%, and the area under the ROC receiver operating characteristic curve AUC was 98.7%. The DERFS-XGBoost model has new characteristics which are different from existing diagnostic models, and has achieved a high classification effect with a small number of genes in comparison tests, which provides a new method and basis for the diagnosis of GC.