Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It's vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

Melatonin activates Nrf2/HO-1 signalling pathway to antagonizes oxidative stress-induced injury via melatonin receptor 1 (MT1) in cryopreserved mice ovarian tissue.

Our previous research has shown that melatonin (MLT) can reduce cryopreserved ovarian damage in mice. Yet, the molecular mechanism of MLT protection is still unclear. Some studies have shown that melatonin receptor 1 (MT1) is very important for animal reproductive system. To evaluate whether MLT exerts its protective effect on cryopreserved mice ovarian tissue via MT1, we added antagonist of MT1/MT2 (Luzindor) or antagonist of MT2 (4P-PDOT) to the freezing solution, followed by cryopreservation and thawing of ovarian tissue. The levels of total superoxide dismutase (T-SOD), catalase (CAT), nitric oxide (NO) and malondialdehyde (MDA) were detected. Besides, by using RT-PCR and Western blotting, the expression of Bcl-2, Bax and Nrf2/HO-1 signalling pathway-related proteins was detected. These findings demonstrated that compared with the melatonin group, the addition of Luzindor increased apoptosis, NO and MDA activities, decreased CAT and T-SOD activities and inhibited Nrf2/HO-1 signalling pathway. In conclusion, melatonin can play a protective role in cryopreserved ovarian tissue of mice through MT1 receptor.

Nanoporous Titanium Implant Surface Accelerates Osteogenesis via the Piezo1/Acetyl-CoA/ß-Catenin Pathway.

Osseointegration is the most important factor determining implant success. The surface modification of TiO2 nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca2+. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of ß-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.

Bioinformatics screening of prognostic immune-related genes in renal clear cell carcinoma.

This study aims to harness bioinformatics to identify prognostic immune-related genes in clear cell renal cell carcinoma (ccRCC), focusing particularly on LILRB3. It evaluates LILRB3's expression in ccRCC, its association with patient prognosis, and its potential as a biomarker for predicting survival, thereby providing a preliminary basis for the diagnosis of ccRCC. Utilizing The Cancer Genome Atlas (TCGA) datasets and an immune gene set, we sought immune-related genes with elevated expression in ccRCC. Seventy-two normal tissue samples and 531 ccRCC samples were analyzed, and differential genes were identified with a screening criterion of fold change (FC) > 2 and P value < 0.01. Survival analysis and receiver operating characteristic (ROC) curve analysis were employed to discover genes of prognostic and diagnostic relevance to ccRCC. Pearson correlation analysis with a cutoff of |r|≥ 0.5, facilitated by cBioPortal, assessed genes co-expressed with LILRB3. The DAVID online tool conducted functional and pathway enrichment analyses for LILRB3-coexpressed genes. The TIMER and TCIA databases were utilized to explore LILRB3's influence on immune infiltration in the tumor microenvironment and its relation to key immunological checkpoints. Screening the TCGA database revealed 3719 up-regulated differential genes in ccRCC, with 355 overlapping immune-related genes. Survival analysis of these 355 genes revealed 100 with significant survival impact. ROC curve analysis pinpointed the top 10 genes, including LILRB3, with the highest diagnostic efficiency. LILRB3 emerged as an independent risk factor from the Cox risk regression model. GO and KEGG analyses linked LILRB3 to various biological processes, including chemokine signaling pathways, immunological response, antigen processing and presentation, inflammatory response, T cell co-stimulation, and signal transduction. LILRB3 significantly affected ccRCC immune infiltration and correlated positively with several immunological checkpoints, such as PD-1, LAG3, IDO1, PD-L1, CTLA4, TIM3, TIGIT, and VISTA. LILRB3 shows higher expression levels in ccRCC than in normal tissues and correlates with poor patient prognosis. Its impactful role in the immune infiltration of the RCC microenvironment suggests that LILRB3 could serve as a novel target for ccRCC treatment and prognosis, underlining its diagnostic and prognostic significance.

Three New Species of Penicillium from East and Northeast China.

Penicillium species are ubiquitous in the environment and are of substantial importance, especially in industrial and medical aspects. During our investigation of the biodiversity of Penicillium, three new species were discovered in soil samples collected from East and Northeast China. They were determined as new to science based on morphological comparisons and phylogenetic analyses, and were found to belong to the subgenus Penicillium section Robsamsonia and subgenus Aspergilloides sections Aspergilloides and Citrina. Descriptions and illustrations of these species are provided, and their geographic distributions are also discussed.

Microbial-induced carbonate precipitation effectively prevents Pb2+ migration through the soil profile: Lab experiment and model simulation.

Due to the inappropriate disposal of waste materials containing lead (Pb) and irrigation with sewage containing Pb, the migration of Pb2+ within the soil profile has been extensively investigated. The conventional Pb2+ block method is challenging to implement due to its complex operational procedures and high construction costs. To address this issue, this study introduces the microbial-induced carbonate precipitation (MICP) technique as a novel approach to impede the migration of Pb2+ in the soil profile. Soil acclimatization with urea resulted in an increased proportion of urease-producing microorganisms, including Bacillus, Paenibacillus, and Planococcaceae, along with heightened expression of urea-hydrolyzing genes (UreA, UreB, UreC, and UreG). This indicates that urea-acclimatized soil (Soil-MICP) possesses the potential to induce carbonate precipitation. Batch Pb2+ fixation experiments confirmed that the fixation efficiency of Soil-MICP on Pb2+ exceeded that of soil without MICP, attributed to the MICP process within the Soil-MICP group. Dynamic migration experiments revealed that the MICP reaction transformed exchangeable lead into carbonate-bound Pb, effectively impeding Pb2+ migration in the soil profile. Additionally, the migration rate of Pb2+ in Soil-MICP was influenced by varying urea amounts, pH levels, and pore flow rates, leading to a slowdown in migration. The Two-site sorption model aptly described the Pb2+ migration process in the Soil-MICP column. This study aims to elucidate the MICP biomineralization process, uncover the in-situ blocking mechanism of MICP on lead in soil, investigate the impact of Pb on key genes involved in urease metabolism, enhance the comprehension of the chemical morphology of lead mineralization products, and provide a theoretical foundation for MICP technology in preventing the migration of Pb2+ in soil profiles.

Intermediate soil acidification induces highest nitrous oxide emissions.

Global potent greenhouse gas nitrous oxide (N2O) emissions from soil are accelerating, with increases in the proportion of reactive nitrogen emitted as N2O, i.e., N2O emission factor (EF). Yet, the primary controls and underlying mechanisms of EFs remain unresolved. Based on two independent but complementary global syntheses, and three field studies determining effects of acidity on N2O EFs and soil denitrifying microorganisms, we show that soil pH predominantly controls N2O EFs and emissions by affecting the denitrifier community composition. Analysis of 5438 paired data points of N2O emission fluxes revealed a hump-shaped relationship between soil pH and EFs, with the highest EFs occurring in moderately acidic soils that favored N2O-producing over N2O-consuming microorganisms, and induced high N2O emissions. Our results illustrate that soil pH has a unimodal relationship with soil denitrifiers and EFs, and the net N2O emission depends on both the N2O/(N2O + N2) ratio and overall denitrification rate. These findings can inform strategies to predict and mitigate soil N2O emissions under future nitrogen input scenarios.

Bactericidal efficacy of lithium magnesium silicate hydrosol incorporated with slightly acidic electrolyzed water in disinfection application against Escherichia coli.

In food safety implementation, bacterial inactivation is an imperative aspect of hygiene and sanitation. Studies on lithium magnesium silicate (LMS) hydrosol incorporated with slightly acidic electrolyzed water (SAEW) for decontamination of pathogenic bacteria are limited. This present study aimed to investigate the bactericidal efficacy of LMS hydrosol incorporated with SAEW against Escherichia coli. Optimum combination conditions of SAEW, hydrosol concentration, and available chlorine concentration (ACC) were optimized by response surface methodology under the central composite design against the growth of E. coli. The optimum combination conditions of exposure time, hydrosol concentration, and ACC were 9.5 minutes, 1.7%, and 20.5 ppm, respectively. The results showed that the increase in ACC led to inactivation in the survival of E. coli compared with the control (p<0.05). It can be concluded that the best combination percentage between SAEW and hydrosol ranged from 1.5-1.7%, in which E. coli was reduced by 4.50 log10 CFU/mL at an ACC of 9.94 ppm. When increasing the ACC to 14.84 ppm, E. coli was reduced by 4.51 log10 CFU/mL compared with the initial number of bacteria (8.20 log10 CFU/mL) in the control group. The number of bacteria was undetected after increasing ACC to 19.93, 25.15, and 29.88 ppm at 10 min. This study suggests that LMS hydrosol incorporated with SAEW could potentially be used as an effective sanitizer.

Global integrative meta-analysis of the responses in soil organic carbon stock to biochar amendment.

Applying biochar to soil has been recognized as a promising practice of climate-smart agriculture, with considerable potential in enhancing soil organic carbon (SOC) sequestration. Previous studies showed that biochar-induced increases in SOC stock varied substantially among experiments, while the explanatory factors responsible for such variability are still not well assessed. Here, we conducted an integrative meta-analysis of the magnitude and efficiency of biochar-induced change in SOC stock, using a database including 476 field measurements at 101 sites across the globe. Biochar amendment increased SOC stock by 6.13 ± 1.62 (95% confidence interval, CI) and 7.01 ± 1.11 (95% CI) Mg C ha-1, respectively, compared to their unfertilized (R0) and mineral nitrogen (N) fertilized (Rn) references. Of which approx. 52% (R0) and 50% (Rn) were contributed directly by biochar-C input. Corresponding biochar carbon efficiencies in R0 and Rn datasets were estimated as 58.20 ± 10.37% and 65.58 ± 9.26% (95% CI), respectively. The change magnitude of SOC stock increased significantly (p < 0.01) with the increasing amount of biochar-C input, while carbon efficiency of biochar showed an opposite trend. Biochar amendment sequestered larger amounts of SOC with higher efficiency in acidic and loamy soils than in alkaline and sandy soils. Biochar amendments with higher C/N ratio caused higher SOC increase than those with lower C/N ratio. Random forest (RF) algorithm showed that accumulative biochar-C input, soil pH, and biochar C/N ratio were the three most-important factors regulating the SOC stock responses. Overall, these results suggest that applying high C/N ratio biochar in acidic soils is a recommendable agricultural practice from the perspective of enhancing organic carbon.

[Clinical observation of virtual reality technology combined with isokinetic strength training for patients after anterior cruciate ligament reconstruction].

OBJECTIVE: To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared. RESULTS: All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05). CONCLUSION: The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.

Genome-Wide Identification of B-Box Gene Family and Expression Analysis Suggest Its Roles in Responses to Cercospora Leaf Spot in Sugar Beet (Beta Vulgaris L.).

The B-box (BBX) protein, which is a zinc-finger protein containing one or two B-box domains, plays a crucial role in the growth and development of plants. Plant B-box genes are generally involved in morphogenesis, the growth of floral organs, and various life activities in response to stress. In this study, the sugar beet B-box genes (hereafter referred to as BvBBXs) were identified by searching the homologous sequences of the Arabidopsis thaliana B-box gene family. The gene structure, protein physicochemical properties, and phylogenetic analysis of these genes were systematically analyzed. In this study, 17 B-box gene family members were identified from the sugar beet genome. A B-box domain can be found in all sugar beet BBX proteins. BvBBXs encode 135 to 517 amino acids with a theoretical isoelectric point of 4.12 to 6.70. Chromosome localization studies revealed that BvBBXs were dispersed across nine sugar beet chromosomes except chromosomes 5 and 7. The sugar beet BBX gene family was divided into five subfamilies using phylogenetic analysis. The gene architectures of subfamily members on the same evolutionary tree branch are quite similar. Light, hormonal, and stress-related cis-acting elements can be found in the promoter region of BvBBXs. The BvBBX gene family was differently expressed in sugar beet following Cercospora leaf spot infection, according to RT-qPCR data. It is shown that the BvBBX gene family may influence how the plant reacts to a pathogen infection.

Effects of sericin on oxidative stress and PI3K/AKT/mTOR signal pathway in cryopreserved mice ovarian tissue.

Ovarian tissue cryopreservation is an effective fertility protective strategy for preadolescent female cancer patients, whose tumor treatment cannot be delayed. In the present study, the effects of sericin, as an antioxidant, on mice ovarian tissue freezing and thawing were investigated. Mice ovarian tissues were cryopreserved and thawed in medium containing 0.5% or 1%sericin (w/v), and 0.1 mM melatonin. Then, the follicular morphology was observed. The levels of antioxidant enzymes were determined, including glutathione (GSH), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT). Moreover, the levels of nitric oxide (NO), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were also tested. Besides, apoptosis-related proteins Bcl-2 and Bax were determined. Our results showed that 1% sericin maintained follicular morphology, inhibited apoptosis, decreased MDA and NO levels, and boosted endogenous antioxidant enzyme levels, while had no significant effect on LDH levels. Furthermore, these effects may be related with the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of Rapamycin (mTOR) signaling pathway, as demonstrated by increased PI3K, p-AKT and mTOR levels. These findings demonstrate that 1% sericin may reduce oxidative stress and protect ovarian tissues during freezing and thawing via PI3K/AKT/mTOR signaling pathway.

Magnitude and efficiency of straw return in building up soil organic carbon: A global synthesis integrating the impacts of agricultural managements and environmental conditions.

Enhancing soil organic carbon (SOC) through straw return (SR) has been widely recommended as a promising practice of climate-smart agriculture. Many studies have investigated the relative effect of straw return on SOC content, while the magnitude and efficiency of straw return in building up SOC stock remain uncertain. Here, we present an integrative synthesis of the magnitude and efficiency of SR-induced SOC changes, using a database comprising 327 observations at 115 sites globally. Straw return increased SOC by 3.68 ± 0.69 (95 % Confidence Interval, CI) Mg C ha-1, with a corresponding C efficiency of 20.51 ± 9.58 % (95 % CI), of which <30 % was contributed directly by straw-C input. The magnitude of SR-induced SOC changes increased (P < 0.05) with increasing straw-C input and experiment duration. However, the C efficiency decreased significantly (P < 0.01) with these two explanatory factors. No-tillage and crop rotation were found to enhance the SR-induced SOC increase, in both magnitude and efficiency. Straw return sequestrated larger amount of C in acidic and organic-rich soils than in alkaline and organic-poor soils. A machine learning random forest (RF) algorithm showed that the amount of straw-C input was the most important single factor governing the magnitude and efficiency of straw return. However, local agricultural managements and environmental conditions were together the dominant explanatory factors determining the spatial differences in SR-induced SOC stock changes. This entails that by optimizing agricultural managements in regions with favorable environmental conditions the farmer can accumulate more C with minor negative impacts. By clarifying the significance and relative importance of multiple local factors, our findings may aid the development of tailored region-specific straw return policies integrating the SOC increment and its environmental side costs.

Inhibition of autophagic flux by the curcumin analog EF-24 and its antiproliferative effect on MCF-7 cancer cells.

5-Bis[(2-fluorophenyl)methylene]-4-piperidinone (EF-24) is a curcumin analog, which was identified for its physiochemical stability and diverse pharmacological functions. In the present study, EF-24 was added to the breast cancer cell line MCF-7 and its cellular effects were characterized. The results indicated that EF-24 possessed antiproliferative and antimigratory activities on MCF-7 cells as determined by MTT assay, wound healing, and transwell assay, respectively. In addition, the autophagosomal vesicles could be detected by acridine orange staining and electron microscope analysis in EF-24-treated cells. Conversion of LC3-I to LC3-II was also investigated following EF-24 treatment of the cells. However, the expression analysis of p62 and LC3 revealed that EF-24 could inhibit autophagic flux in MCF-7 cells. Confocal microscopy suggested that EF-24 could inhibit the degradation of autophagic vesicles by blocking the fusion of autophagosomes with lysosomes. EF-24 could also induce apoptosis of MCF-7 cells as determined by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. Moreover, treatment of the cells with the autophagy inhibitor 3-MA enhanced the PARP1 cleavage of EF-24-treated MCF-7 cells, which indicated the crosstalk between autophagy and apoptosis in breast cancer cells. Additional investigation of EF-24 should be performed in future studies to assess its antiproliferation and antimigratory effects on MCF-7 cells. However, the current results provide a solid foundation for the potential in vivo anticancer activity of this compound.

Sirtuin3 Alleviated Influenza A Virus-Induced Mitochondrial Oxidative Stress and Inflammation in Lung Epithelial Cells via Regulating Poly (ADP-Ribose) Polymerase 1 Activity.

INTRODUCTION: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children. METHODS: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry. RESULTS: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury. CONCLUSION: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells.

Application of microbial-induced carbonate precipitation (MICP) techniques to remove heavy metal in the natural environment: A critical review.

The occurrence of imbalanced heavy metals concentration due to anthropogenic hindrances in the aquatic and terrestrial environment has become a potential risk to life after circulating through different food chains. The microbial-induced carbonate precipitation (MICP) method has gradually received great attention from global researchers but the underlying mechanism of heavy metal mineralization is not well-understood and challenging, limiting the applications in wastewater engineering. This paper reviews the metabolic pathways, mechanisms, operational factors, and mathematical/modeling approaches in the MICP process. Subsequently, the recent advancement in MICP for the remediation of heavy metal pollution is being discussed. In the follow-up, the key challenges and prospective associated with technical bottlenecks of MICP method are elaborated. The prospective study reveals that MICP technology could be efficiently used to remediate heavy metal contaminants from the natural environment in a cost-effective way and has the potential to improve soil properties while remediating heavy metal contaminated soil.

Preparation of Highly Durable Reverse-Mode Polymer-Stabilized Liquid Crystal Films with Polymer Walls.

Reverse-mode polymer-stabilized liquid crystal (PSLC) films have wide applications in smart windows for cars as well as buildings and dimming glasses due to their low haze, low energy consumption, and better safety in case of emergency power off. However, PSLC films usually have poor stability of electro-optical properties due to their low polymer content (ca. 5 wt %), and it still remains a challenging task to improve the stability and processability by increasing the polymer content in PSLC as the driving voltage might dramatically increase. In this work, a reverse-mode PSLC film with polymer walls was prepared, which showed excellent stability of electro-optical properties even after 150 000 cycles. The film was prepared through polymerization with a photomask, in which the monomers concentrated on specific areas to form patterned polymer walls. In this way, the polymer content could be increased dramatically and the anchoring effect would not be too strong, thus avoiding a sharp increase in the driving voltage. As a result, the desired reverse-mode film with high stability, relatively low driving voltage, and high contrast ratio was obtained. The effects of monomer compositions, curing temperature, UV light intensity, and the pattern of the photomask on the microstructures, as well as electro-optical performances of the films were carefully studied. This work provides a new idea for the preparation of reverse-mode electrically switchable light-transmittance controllable films with excellent stability and good electro-optical performance, which would broaden their application in smart cars, building windows, and dimming glasses for light management and potential energy saving.

A systematic review and network meta-analysis of the efficacy and safety of third-line and over third-line therapy after imatinib and TKI resistance in advanced gastrointestinal stromal tumor.

Tyrosine kinase inhibitors (TKIs) have greatly improved the prognosis of unresectable and metastatic gastrointestinal stromal tumors (GISTs) in the last two decades. Imatinib and sunitinib are recommended as first-line and second-line therapies, respectively. However, there is a lack of precision therapy for refractory GISTs regarding therapy after imatinib and sunitinib. We comprehensively searched electronic databases, including PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials, from inception to October 2022. Randomized controlled trials featuring comparisons with third-line or over third-line therapies against GISTs were eligible. The primary outcome was progression-free survival (PFS). All network calculations were performed using random effect models, and the ranking of regimens were numerically based on the surface under the cumulative ranking (SUCRA) statistics. A total of seven studies were eligible for inclusion in this network meta-analysis. After analysis, ripretinib was ranked at the top in progression-free survival (PFS), overall survival (OS), and disease control rate (DCR) (SUCRA statistics: 83.1%, 82.5%, and 86.5%, respectively), whereas nilotinib and pimitespib presented better tolerability (SUCRA statistics: 64.9% and 63.8%, respectively). We found that regorafenib seemed more reliable for clinical administration, and ripretinib showed good effectiveness for the over third-line therapy. Precise targeted therapy is a critical direction for the future treatment of GIST, and more high-quality studies of new agents are expected.

Clinical Value of Long Non-Coding RNA HOTAIR in Carotid Artery Stenosis and Its Role in Vascular Smooth Muscle Cell Proliferation.

This study investigated the clinical role of HOTAIR in patients with carotid artery stenosis (CAS) and its mechanism in vascular smooth muscle cells (VSMCs). Patients with CAS were collected. The expression of HOTAIR was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical importance of HOTAIR was revealed by the receiver operating characteristic curve. Overexpression and knockdown of HOTAIR were achieved by transfecting pCDNA3.1-HOTAIR plasmid and si-HOTAIR respectively. CCK-8 assay or Transwell assay were used to analyze the changes in cell viability or migration after transfection treatments. Double luciferase reporter gene assay confirmed the targeted relationship between HOTAIR and miR-148b-3p. The levels of miR-148b-3p in VSMCs and patients were detected by qRT-PCR. Pearson analysis was used to analyze the relationship between HOTAIR and miR-148b-3p in patients with CAS. The expression of HOTAIR in patients with CAS was significantly higher than that in healthy individuals. HOTAIR appeared to discriminate CAS patients from healthy people. The overexpression of HOTAIR increased the viability and migration of VSMCs. Silenced HOTAIR restricted the abnormal viability and migration of VSMCs. A double luciferase reporter revealed a region of complementary binding between HOTAIR and miR-148b-3p. The expression of miR-148b-3p in VSMCs was regulated by the levels of HOTAIR. Reduction of miR-148b-3p expression was substantiated in CAS patients. Pearson analysis exhibited that the expression of HOTAIR was negatively relative to the levels of miR-148b-3p. The long noncoding RNA HOTAIR might be a diagnostic biomarker for CAS patients, and it was involved in the activity of vascular smooth muscle cells.

SERPINA1 Methylation Levels are Associated with Lung Cancer Development in Male Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1ß, IL-17, and transforming growth factor (TGF)-ß1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1ß levels (r = 0.5188, p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1ß levels. These findings may be of diagnostic value.