Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer.

Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A's implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.

Case Report: Semi-Ex Vivo Hepatectomy Combined with Autologous Liver Transplantation for Alveolar Echinococcosis in Children.

Hepatic alveolar echinococcosis (AE) is a zoonotic disease caused by the metacestode of Echinococcus multilocularis. Although surgical resection is the optimal treatment for hepatic AE, some patients with hepatic AE located in special introhepatic sites cannot be radically cured by conventional surgery. Here, we report that a 10-year-old female patient was admitted to the hospital with occupying liver lesions for 6 months. Computed tomography examination showed irregular mixed-density masses in the right lobe and caudate lobe of the liver, with partial invasion of the right hepatic artery, right hepatic vein, and right branch of the portal vein. The patient was preoperatively diagnosed with hepatic AE, which cannot be cured by conventional liver lobectomy. The patient underwent semi-ex vivo liver resection with autologous liver transplantation (second hepatic portal reconstruction, posterior hepatic inferior vena cava repair, and hepatic artery repair) and biliary-intestinal anastomosis. After hospital discharge, she has kept living a healthy life without disease recurrence for 13 months until the end of the last follow-up. This case shows that semi-ex vivo hepatectomy with autologous liver transplantation might be a feasible and safe choice for certain patients with AE located in special introhepatic sites, which has provided novel experiences for the surgical treatment of hepatic AE.

High-Performance Bamboo Steel Derived from Natural Bamboo.

It is highly desirable to develop green and renewable structural materials from biomaterials to replace synthetic materials involved from civil engineering to aerospace industries. Herein, we put forward a facile but effective top-down strategy to convert natural bamboo into bamboo steel. The fabrication process of bamboo steel involves the removal of lignin and hemicellulose, freeze-drying followed by epoxy infiltration, and densification combined with in situ solidification. The prepared bamboo steel is a super-strong composite material with a high specific tensile strength (302 MPa g-1 cm3), which is higher than that (227 MPa g-1 cm3) of conventional high specific strength steel. The bamboo steel demonstrates a high tensile strength of 407.6 MPa, a record flexural strength of 513.8 MPa, and a high toughness of 14.08 MJ/m3, which is improved by 360, 290, and 380% over those of natural bamboo, respectively. Particularly, the mechanical properties of the bamboo steel are the highest among the biofiber-reinforced polymer composites reported previously. The well-preserved bamboo scaffolds assure the integrity of bamboo fibers, while the densification under high pressure results in a high-fiber volume fraction with an improved hydrogen bonding among the adjacent bamboo fibers, and the epoxy resin impregnated enhances the stress transfer because of its chemical crosslinking with cellulose molecules. These endow the bamboo steel with superior mechanical performance. Furthermore, the bamboo steel demonstrates an excellent thermal insulating capability with a low thermal conductivity (about 0.29 W/mK). In addition, the bamboo steel shows a low coefficient of thermal expansion (about 6.3 × 10-6 K-1) and a very high-dimensional stability to moisture attack. The strategy of fabricating high-performance bamboo steel with green and abundant natural bamboo as raw materials is highly attractive for the sustainable development of structural engineering materials.

Ultra-performance liquid chromatography/mass spectrometry technology and high-throughput metabolomics for deciphering the preventive mechanism of mirabilite on colorectal cancer via the modulation of complex metabolic networks.

Colorectal cancer (CRC) is a highly virulent and malignant disease and always accompanied by metabolic disorders. Currently, there are no effective therapeutic drugs for the treatment of CRC. High-throughput metabolomics approaches have been used to unveil the metabolic pathways related to several diseases. In this study, ultra-performance liquid chromatography/mass spectrometry-based high-throughput metabolomics was used for deciphering the potential preventive mechanism of mirabilite on CRC via the modulation of the associated metabolic disorders; a total of 28 differential biomarkers, including indole acetaldehyde, 5-hydroxyindoleacetic acid, hypoxanthine, retinal, retinal ester, linoleic acid, stearic acid, 6-deoxocastasterone, 2-hydroxybutyric acid and LysoPC, were identified in the APCmin/+ mice. These differential biomarkers are involved in the tryptophan metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Note that these biomarkers and their disturbed metabolic pathways were also regulated by mirabilite. It has been found that the prevention of CRC by mirabilite is mainly associated with tryptophan metabolism; this study shows that high-throughput metabolomics can reveal the perturbed metabolic disorders targeted in the action mechanism of drug treatment.

Network pharmacology combined with functional metabolomics discover bile acid metabolism as a promising target for mirabilite against colorectal cancer.

In this study, a combination of network pharmacology and metabolomics was used to explore the mechanism by which mirabilite regulates bile acid metabolism in the treatment of colorectal cancer. The PharmMapper web server was applied to make preliminary predictions for the treatment targets of mirabilite and to predict the interaction between mirabilite and disease targets using Discovery Studio 2.5. Furthermore, the urine metabolic profile was analyzed by the UPLC-Q-TOF-MS technology. The original data were processed by Progenesis QI software and analyzed by multivariate pattern recognition, which allowed us to reveal the metabolic disturbance in colorectal cancer and explain the therapeutic effect of mirabilite. The network pharmacology results showed that mirabilite can act on the disease targets, and the sites of action include amino acid residues Arg-364 and Asp-533, as well as nucleotides TPC-11, DG-112 and DA-113. Based on metabolomics, potential biomarkers were found to lie in the relevant pathways of bile acid metabolism, such as taurine, chenodeoxycholic acid, cholic acid, and deoxycholic acid. The results showed that mirabilite could regulate the distribution of overall metabolic disturbance, and bile acid metabolism was the main targeted pathway. Additionally, we predicted the upstream targets by ingenuity pathway analysis and found that mirabilite played a significant role in regulating the bile acid-related biomarkers, which allowed comprehensive analysis of the effect of mirabilite on colorectal cancer. This study fully explained the role of mirabilite in inhibiting colorectal cancer, which mainly occurs through bile acid metabolism, via the approach of network pharmacology combined with functional metabolomics.

High-throughput lipidomics reveal mirabilite regulating lipid metabolism as anticancer therapeutics.

Altered lipid metabolism is an emerging hallmark of cancers. Mirabilite has a therapeutic effect on colorectal cancer (CRC); however, its metabolic mechanism remains unclear. This study aims to explore the potential therapeutic targets of mirabilite protection against colorectal cancer in APCmin/+ mice model. Oral administration of mirabilite was started from the ninth month, while the same dosage of distilled water was given to both the control group and the model group. Based on lipidomics, we collected serum samples of all mice at the 20th week and used a non-targeted method to identify the lipid biomarkers of CRC. Compared with C57BL/6J mice, the metabolic profile of CRC model mice was significantly disturbed, and we identified that 25 lipid-related biomarkers, including linoleic acid, 2-hydroxybutyric acid, 6-deoxocastasterone, hypoxanthine, PC(16:1), PC(18:4), and retinyl acetate, were associated with CRC. According to the abovementioned results, there were six lipid molecules with significant differences that can be used as new targets for handling of CRC through six metabolic pathways, namely, linoleic acid metabolism, retinol metabolism, propanoate metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and purine metabolism. Compared with the model group, the metabolic profiles of these disorders tend to recover after treatment. These results indicated that the lipid molecules associated with CRC were regulated by mirabilite. In addition, we identified seven key lipid molecules, of which four had statistical significance. After administration of mirabilite, all disordered metabolic pathways showed different degrees of regulation. In conclusion, high-throughput lipidomics approach revealed mirabilite regulating the altered lipid metabolism as anticancer therapeutics.

Serum cystatin C level is associated with carotid intima-media thickening and plaque.

BACKGROUND AND AIM: Chronic kidney disease has recently been shown to be a major risk factor for cardiovascular disease and carotid intima-media thickness has been widely used as a biomarker for early detection of cardiovascular disease. The aim of this study was to confirm whether carotid thickening and carotid plaque are associated with preclinical chronic kidney disease in individuals without clinical cardiovascular disease and chronic kidney disease. MATERIAL AND METHODS: We conducted a cross-sectional study on participants from Maanshan City, China. All participants underwent carotid ultrasonography. Kidney function was measured using cystatin C, serum creatinine, blood urea nitrogen and blood uric acid. Demographics and risk factors for cardiovascular diseases were obtained from each participant. RESULTS: A total of 927 subjects were surveyed; 453 (48.87%) were men and 474 (51.13%) were women. A total of 525 (56.63%) of the participants were found to have carotid thickening of which 281 (53.52%) were men and 244 (46.48%) were women. Kidney function was strongly associated with carotid thickening and plaque in the unadjusted analysis. However, cystatin C was the only measure of kidney function that was significantly associated with carotid thickening and plaque in the adjusted analysis (in order to select risk factors from sex, age, BMI, hypertension, diabetes, smoking, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein A, apolipoprotein B, cystatin C, creatinine, blood urea nitrogen, blood uric, estimated GFR). CONCLUSION: Cystatin C, an alternative measure of kidney function, was more strongly associated with carotid thickening and plaque than other measures of kidney function.

[Combined three-dimensional conformal radiotherapy plus transcatheter arterial chemoembolization and surgical intervention for portal vein tumor thrombus in patients with hepatocellular carcinoma].

OBJECTIVE: To explore the clinical therapeutic efficacies of combined three-dimensional conformal radiotherapy (3DCRT) plus transcatheter arterial chemoembolization (TACE) for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC). METHODS: A total of 145 HCC patients with tumor thrombus in portal vein were divided randomly into 2 groups. Group A (n = 64) was treated with surgical intervention alone while group B (n = 81) underwent 3DCRT plus TACE. The gross tumor volume (GTV) was defined as PVTT only. RESULTS: Survival rates of group A at year 1 and 2 were 40.3% and 21.9% with a mean survival time (MST) of 15.2 months while that of group B were 41.2% and 22.5% with a MST of 15.8 months. The total effective rates of groups A and B was 40.6% (28/64) and 44.4% (36/81) respectively. CONCLUSION: The therapeutic efficacy of 3DCRT plus TACE is similar to that of surgical intervention.