Noncoding RNA Linc00475 promotes the proliferation of colorectal cancer cells by targeting miR-107/CDK6 axis.

Colorectal cancer (CRC) represents a substantial challenge to public health. Despite extensive research, the pathogenesis of CRC is not yet fully elucidated, hindering the development of effective therapeutic strategies. Recent advancements have underscored the importance of Non-coding RNAs in tumor biology. Our research identified a significant upregulation of Linc00475 in CRC, which correlated with reduced survival rates among CRC patients. Consequently, this study aimed to elucidate the mechanisms by which Linc00475 contributed to CRC progression. Employing a comprehensive array of experimental techniques-including CCK-8 assays, colony formation assays, flow cytometry, quantitative PCR (qPCR), western blot analysis, and in vivo tumorigenesis assays-we have demonstrated that Linc00475 enhances CRC cell proliferation. Further analysis revealed that Linc00475 directly interacted with miR-107, leading to its downregulation. Moreover, our findings confirmed that miR-107 directly targeted CDK6, which was markedly downregulated following Linc00475 silencing. In vivo experiments further indicated that the silencing of Linc00475 markedly inhibited the proliferation of CRC cells. Collectively, our findings suggested that Linc00475 facilitated CRC cell proliferation through the regulation of the miR-107/CDK6 axis, thereby providing a novel perspective for understanding the molecular mechanisms underlying CRC development.

A Nomogram to Predict the Overall Survival of Patients With Resected T1-2N0-1M0 Non-Small Cell Lung Cancer and to Identify the Optimal Candidates for Adjuvant Chemotherapy in Stage IB or IIA Non-Small Cell Lung Cancer Patients.

BACKGROUND: The benefit of adjuvant chemotherapy for IB/IIA non-small cell lung cancer (NSCLC) patients remains uncertain. This study aimed to develop a prognostic model to predict overall survival in resected NSCLC patients with T1-2N0-1M0 stage and identify optimal candidates for postoperative chemotherapy among those with stage IB or IIA disease. METHODS: We conducted a retrospective study using the SEER 18 database (2000-2018, November 2020 submission) of patients who underwent radical surgery for T1-2N0-1M0 NSCLC. The patients not receiving adjuvant chemotherapy were randomly divided into training and validation cohorts. A prognostic nomogram was established and evaluated using calibration and receiver operating characteristic curves. Based on the nomogram, stage IB and IIA patients were categorized into two prognostic groups, each further divided into cohorts based on adjuvant chemotherapy status. Kaplan-Meier analysis and log-rank tests were used to compare overall survival between these groups. RESULTS: A total of 14 789 patients were enrolled and randomly assigned to the training cohort (n = 10 352) and validation cohort (n = 4437). Ten independent prognostic factors were identified and integrated into the prognostic model. The area under the receiver operating characteristic curve was .706, .699, and .705 in the training cohort, and .700, .698, and .695 in the validation cohort at 1, 3, and 5 years, respectively. Among stage IB and IIA patients, only those in the high-risk group showed a significant benefit from adjuvant chemotherapy, with a 16.4% absolute increase in 5-year overall survival. CONCLUSIONS: The nomogram developed in the study may help physicians choose the most appropriate management strategy for each patient.

Adenovirus infection diagnosed by metagenomic next-generation sequencing after haploidentical hematopoietic stem cell transplantation: A multicenter study in China.

OBJECTIVE: This study aims to observe and analyze the clinical characteristics and prognosis of adenovirus (ADV) infection diagnosed by metagenomic next-generation sequencing (mNGS) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), which was performed following Beijing Protocol. METHODS: The clinical data of patients who developed ADV infection diagnosed by mNGS after Haplo-HSCT between January 2019 and March 2021, recorded in three transplantation centers, were retrospectively analyzed. Potential risk factors for infection and the clinical manifestations of ADV involvement in different end-organs were also studied. Additionally, the patient prognosis regarding the available treatment was observed. RESULTS: A total of seven patients were diagnosed with ADV infection by the mNGS technique after Haplo-HSCT of 976 patients enrolled. The risk factors for infection included antithymocyte globulin steroid-refractory graft-versus-host disease (GVHD) history, CD25 monoclonal antibody or ruxolitinib treatment history and <300 cells/µL of CD3+ T cells count in peripheral blood. The clinical manifestations of ADV infection included encephalitis, hepatitis, cystitis, and pneumonia. Six patients were treated with cidofovir (CDV) and intravenous immunoglobulin (IVIg), and one with CDV, ribavirin, IVIg, thymosin Alpha-1 for injection and low-dose donor lymphocyte infusion. One case showed negative ADV DNA results with improved conditions; however, the patient died of the relapse of the primary disease in the later stage. The remaining six died of ADV infection. CONCLUSION: mNGS can provide screening for ADV and information on ADV subtypes, helpful to understand tissue tropism. This technique could be useful in diagnosing patients at high risk for ADV infection. ADV infection can involve multiple organs, has difficulty in early diagnosis, and has a poor prognosis. Currently, effective treatments are inadequate.

P-Y/G@NHs sensitizes non-small cell lung cancer cells to radiotherapy via blockage of the PI3K/AKT signaling pathway.

Radioresistance represents a common phenomenon found in cancer treatment. Herein, the current study sought to evaluate the effects of a nanodrug delivery system of YSAYPDSVPMMS (YSA) peptide-modified gold nanoparticles-dextran-based hydrogel loaded with paclitaxel-succinic anhydride (P-Y/G@NHs) on non-small cell lung cancer (NSCLC) cell radiosensitivity. Firstly, utilizing the coupling reaction and layer-by-layer assembly technique, P-Y/G@NHs was prepared. The therapeutic effects of the P-Y/G@NHs in NSCLC cells in relation to the PI3K/AKT signaling pathway were examined by assessing the colony formation, apoptosis, and reactive oxygen species (ROS) generation of A549 cells under 10 Gy X-rays irradiation. Moreover, A549 tumor-bearing mice were generated to further validate the therapeutic effect in vivo. We confirmed the successful conjugation of the nanocomposite. Under 10 Gy X-rays irradiation, P-Y/G@NHs reduced the number of colonies of A549 cells, while inducing both cell apoptosis and ROS production. Moreover, P-Y/G@NHs enhanced the radiosensitivity of A549 cells by inhibiting the PI3K/AKT signaling pathway. In vivo fluorescence experiments validated that P-Y/G@NHs effectively-targeted and accumulated at the tumor site in nude mice, thus augmenting the radiosensitivity of tumors without significant immune toxicity or side effects. Conclusively, our findings highlighted that P-Y/G@NHs significantly enhanced the radiosensitivity of NSCLC cells by repressing the PI3K/AKT signaling pathway.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Clinical evaluation of deep learning-based clinical target volume three-channel auto-segmentation algorithm for adaptive radiotherapy in cervical cancer.

OBJECTIVES: Accurate contouring of the clinical target volume (CTV) is a key element of radiotherapy in cervical cancer. We validated a novel deep learning (DL)-based auto-segmentation algorithm for CTVs in cervical cancer called the three-channel adaptive auto-segmentation network (TCAS). METHODS: A total of 107 cases were collected and contoured by senior radiation oncologists (ROs). Each case consisted of the following: (1) contrast-enhanced CT scan for positioning, (2) the related CTV, (3) multiple plain CT scans during treatment and (4) the related CTV. After registration between (1) and (3) for the same patient, the aligned image and CTV were generated. Method 1 is rigid registration, method 2 is deformable registration, and the aligned CTV is seen as the result. Method 3 is rigid registration and TCAS, method 4 is deformable registration and TCAS, and the result is generated by a DL-based method. RESULTS: From the 107 cases, 15 pairs were selected as the test set. The dice similarity coefficient (DSC) of method 1 was 0.8155 ± 0.0368; the DSC of method 2 was 0.8277 ± 0.0315; the DSCs of method 3 and 4 were 0.8914 ± 0.0294 and 0.8921 ± 0.0231, respectively. The mean surface distance and Hausdorff distance of methods 3 and 4 were markedly better than those of method 1 and 2. CONCLUSIONS: The TCAS achieved comparable accuracy to the manual delineation performed by senior ROs and was significantly better than direct registration.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

Abiraterone suppresses irradiated lung cancer cells-induced angiogenic capacities of endothelial cells.

Non-small cell lung cancer (NSCLC) threatens human life globally with high morbidity and mortality and radiotherapy is one of the most effective methods for the treatment of NSCLC. However, it is currently reported that the angiogenesis of tumors can be induced by a low dosage of irradiation. Abiraterone is an oral anti-tumor agent for the treatment of castration-resistant prostate cancer (CRPC). In the present study, the anti-angiogenesis effect of Abiraterone against HUVECs incubated with irradiated lung cancer cell medium will be investigated. The HUVECs were incubated with a cultural medium of the NSCLC cell line-A549, Abiraterone-treated A549 cells, irradiation-treated A549 cells, and Abiraterone and irradiation co-treated A549 cells. The tolerable concentration of Abiraterone against HUVECs was determined using MTT assay. The migration and angiogenesis abilities of HUVECs were evaluated using transwell and tube formation assays, respectively. The expression levels of VEGF, MMP-2, and MMP-9 in the treated HUVECs were detected using qRT-PCR and ELISA. Western blot was used to determine the expressions of p-PI3K and p-AKT. The tolerable concentration of Abiraterone used in the present study was 50 nM. First, the migration rate and numbers of formed tubes were significantly decreased by the A549 medium treated with Abiraterone and elevated by the A549 medium treated with irradiation but greatly suppressed by the co-treatment with Abiraterone. Subsequently, VEGF, MMP-2, and MMP-9 were significantly downregulated by the A549 medium treated with Abiraterone and upregulated by the A549 medium treated with irradiation but greatly inhibited by the co-treatment with Abiraterone. Lastly, the activated PI3K/AKT signaling pathway induced by the A549 medium treated with irradiation was significantly suppressed by the A549 medium treated with both irradiation and Abiraterone. Abiraterone suppressed irradiated lung cancer cells-induced angiogenic capacities of endothelial cells.

The Combination of Preoperative Nutritional Risk Screening-2002 and Neutrophil-to-Lymphocyte Ratio is a Useful Prognostic Marker in Patients with Esophageal Squamous Cell Carcinoma.

The aim of this study was to investigate the prognostic values of a novel evaluated system, named the CONN (combination of Nutritional Risk Screening 2002 [NRS-2002] and neutrophil-to-lymphocyte ratio [NLR]), in patients with esophageal squamous cell carcinoma (ESCC) by curative esophagectomy. A total of 278 patients with ESCC receiving standard curative esophagectomy were retrospectively analyzed. The CONN was calculated by combined NRS-2002 and NLR according to the corresponding cutoff values: patients with both elevated NRS-2002 (≥3.0) and NLR (≥3.0) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. In our univariate analysis, the following factors were significantly associated with poor PFS and OS: T stage, N stage, TNM stage, NLR, NRS-2002 and CONN (all P < 0.05). Furthermore, multivariate Cox regression analysis showed that N stage (P = 0.039), NRS-2002 (P = 0.041) and CONN (P = 0.001) were independent prognostic factors for PFS. While T stage (P = 0.017), N stage (P = 0.048), NLR (P = 0.021), NRS-2002 (P = 0.001) and CONN (P = 0.001) were independent prognostic factors for OS. In conclusion, CONN was an independent prognostic marker for survival prediction in patients with ESCC receiving surgery.

Low optical dosage heating-reduced viscosity for fast and large-scale cleanup of spilled crude oil by reduced graphene oxide melamine nanocomposite adsorbents.

Heating under low solar radiation intensity is demonstrated to facilitate the cleaning of crude oil by the hydrophobic nanocomposite adsorbents of reduced graphene oxide (RGO) melamine sponge (MS@RGO) foams. The heat generated by the irradiation reduces the viscosity of the crude oil, and consequently increases the oil-diffusion coefficient of the pores of the MS@RGO foams and speeds up the oil-sorption rate. Even under a solar radiation intensity as low as 2 kW m-2, the temperature of crude oil rapidly rises to 68 °C or higher within 10 min. It only takes 29 s to completely absorb 6 g of crude oil at 60 °C by three tiny pieces of MS@RGO foam. This work makes better use of the excellent photothermal conversion characteristics of crude oil, and its photothermal conversion mechanism under simulated solar radiation is also discussed. This methodology can be adopted to clean up viscous crude oil or extract other chemicals effectively at a large scale, and provides a complete solution for the cleanup of crude oil in the sea or on the beach for actual engineering applications.

PIK3C3 Acts as a Tumor Suppressor in Esophageal Squamous Cell Carcinoma and Was Regulated by MiR-340-5p.

BACKGROUND Esophageal squamous cell carcinoma (ESCC), a major histological subtype of esophageal cancer, is a common cause of tumor-related deaths in the world. Due to the lack of understanding of the pathogenesis of ESCC, its clinical treatment is still a big challenge. In the present study, we aimed to identify an ESCC-related gene in the GEO dataset, and to explore its function and mechanism in ESCC. MATERIAL AND METHODS The GSE dataset (GSE100492) consisting of 10 samples was analyzed using GEO2R for identifying the differentially expressed genes between ESCC and normal samples. Expression levels of mRNA and miRNA in ESCC tissues and cells were detected via quantitative real-time polymerase chain reaction. Protein expression was analyzed by western blot. Cell proliferation viability was determined through MTT and colony formation. Cell distribution and apoptosis was detected by flow cytometry. MiRNA target prediction was analyzed by bioinformatics. The interplay between miR-340-5p and PIK3C3 was validated by dual-luciferase reporter assay. RESULTS PIK3C3 was lowly expressed in ESCC tissue and indicated a poor prognosis in patents. Overexpression of PIK3C3 in vitro repressed cell proliferation of KYSE-150 and TE-12 cells. Moreover, PIK3C3 overexpression was demonstrated to enhance the sensitivity of KYSE-150 and TE-12 cells to irradiation. In addition, miR-340-5p was revealed to directly bind and negatively modulate PIK3C3 expression in ESCC. Blockage of miR-340-5p promoted ESCC cell proliferation, while rescue of PIK3C3 reversed this effect. MiR-340-5p was highly expressed in ESCC tissue and it exhibited a negative correlation with PIK3C3 expression. CONCLUSIONS MiR-340-5p functioned as an oncogene of ESCC by directly binding and repressing the expression of PIK3C3.

The Construction of a Radiation-Induced Brain Injury Model and Preliminary Study on the Effect of Human Recombinant Endostatin in Treating Radiation-Induced Brain Injury.

BACKGROUND The aim of this study was to construct a radiation-induced brain injury (RBI) model and assess the effects of human recombinant endostatin in the treatment of RBI. MATERIAL AND METHODS In this study, the RBI model was used. Real-time quantitative polymerase chain reaction, immunohistochemistry, hematoxylin and eosin staining were conducted to detect the mRNA and protein expression of vascular endothelial growth factor (VEGF) and assess the effects of human recombinant endostatin in the treatment of RBI. RESULTS In this study, we successfully constructed a RBI model. VEGF mRNA expression was decreased after human recombinant endostatin treatment; however, VEGF protein secretion was increased in brain endothelial cells, and the secretion of VEGF protein was decreased in glial cells and nerve cells. Body weight changes indicated that human recombinant endostatin can increase the risk of weight loss. Brain water content results showed that human recombinant endostatin might aggravate cerebral edema in the acute stage of RBI, but it can reduce the progression of cerebral edema in the early delayed stage. Survival analysis showed that human recombinant endostatin improved the survival rate only in the early stage of RBI. CONCLUSIONS Radiation can induce vasogenic edema and is associated with the RBI occurrence and development. VEGF protein is highly relevant to the induction of edema and thrombosis in the acute phase of RBI and in the early delayed phase of RBI, including vascular repair and regeneration, thrombus ablation and other events. Human recombinant endostatin can reduce the progression of cerebral edema during the early onset of RBI.

First Application of Demand-Triggered Online Adaptive Radiotherapy in the Treatment of Cervical Cancer: A Clinical Report.

Gynecology cancers can reap significant benefits from adaptive radiation therapy (ART) for four major reasons: organ motion, organ deformation, density change, and cavity filling. There are three recognized types of adaptive radiotherapy: offline, online, and real-time. This balance of improved dosimetry versus clinic resources, as well as the optimal timing for adaptations, is still under investigation. The emergence of on-demand online adaptive radiotherapy (OART) can solve the above problems. In this context, we introduce two patients with cervical cancer who used on-demand OART for the first time. One patient with cervical cancer received radical radiotherapy on the United Imaging uCT-ART platform, and another patient with cervical cancer received postoperative adjuvant radiotherapy. The radiotherapy process used OART, which was triggered by senior radiotherapists, assisted by artificial intelligence, and guided by fan-beam computer tomography. Patient 1, who was 54 years old with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage ⅢC1, underwent radical concurrent chemoradiotherapy. The target volume was reduced in the late stage of radiotherapy. The target volume coverage of the OART plan was better, and the bladder and rectum doses were lower than those of the image-guided radiotherapy plan. Patient 2, who was 56 years old with cervical adenocarcinoma, FIGO stage ⅡA1, underwent postoperative concurrent chemoradiotherapy. If the fractionated treatment during radiotherapy was carried out according to the original plan, treatment off-target would occur, while the OART plan could ensure target coverage. The acute toxic reactions that occurred in both patients during radiotherapy were patient-reported outcome Common Terminology Criteria for Adverse Events 1-2, and no toxic reactions of grade 3 or above occurred. This is the first description of the successful implementation of the uCT-ART-based OART system in EBRT for cervical cancer.

Microbiome profiling and Co-metabolism pathway analysis in cervical cancer patients with acute radiation enteritis.

Background: Intestinal bacteria significantly contribute to the metabolism of intestinal epithelial tissues. As the occurrence and development of radiation enteritis (RE) depend on the "co-metabolism" microenvironment formed by the host and intestinal microbiota, which involves complex influencing factors and strong correlations, ordinary techniques struggle to fully explain the underlying mechanisms. However, given that it is based on systems biology, metabolomics analysis is well-suited to address these issues. This study aimed to analyze the metabolomic changes in urine, serum, and fecal samples during volumetric modulated arc therapy (VMAT) for cervical cancer and screen for characteristic metabolites of severe acute radiation enteritis (SARE) and RE. Methods: We enrolled 50 patients who received radiotherapy for cervical cancer. Urine, serum, and fecal samples of patients were collected at one day before radiotherapy and the second week, fourth week, and sixth week after the start of radiotherapy. Control group samples were collected during the baseline period. Differential metabolites were identified by metabolomics analysis; co-metabolic pathways were clarified. We used the mini-SOM library for incorporating characteristic metabolites, and established metabolite classification models for predicting SARE and RE. Results: Urine and serum sample data showed remarkable clustering effect; metabolomics data of the fecal supernatant were evidently disturbed. Patient sample analyses during VMAT revealed the following. Urine samples: Downregulation of the pyrimidine and riboflavin metabolism pathways as well as initial upregulation followed by downregulation of arginine and proline metabolism pathways and the arginine biosynthesis pathway. Fecal samples: Upregulation of linoleic acid and phenylalanine metabolic pathways and initial downregulation followed by upregulation of arachidonic acid (AA) metabolic pathways. Serum samples: Initial upregulation followed by downregulation of the arginine biosynthesis pathway and downregulation of glutathione, AA, and arginine and proline metabolic pathways. Conclusion: Patients with cervical cancer exhibited characteristic metabolic pathways and characteristic metabolites predicting RE and SARE were screened out. An effective RE mini-SOM classification model was successfully established.

Effect of Raltitrexed on ECA109 Cellular Radiosensitivity and its Mechanism in Esophageal Cancer.

BACKGROUND: To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer ECA109 cells and analyze the potential action mechanism. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer, and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated X protein (Bax) in each group. RESULTS: Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there were significant differences among different concentrations and times of action. The results of the clone-forming experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect. After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number of cells penetrating the membrane was reduced. CONCLUSION: Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization effect.

Network toxicological and molecular docking to investigate the mechanisms of toxicity of agricultural chemical Thiabendazole.

Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole's potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals.

Efficacy and Safety Analysis of Recombinant Human Endostatin (Endostar) Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer: A 2-Center Retrospective Study.

BACKGROUND: This study aims to assess the efficacy and safety of Endostar in the management of locally advanced cervical cancer. METHODS: This retrospective, 2-center study enrolled 41 patients with locally advanced cervical cancer between June 2017 and December 2020. The patients were subjected to a combination of Endostar and chemoradiotherapy until they experienced disease progression or an unacceptable level of toxicity. The patients in the Endostar combined chemoradiotherapy (E + CRT) and CRT groups were matched 1:1 based on clinical features, including age, disease stage, and pathological type. The therapeutic efficacy and safety outcomes were compared between the 2 groups. RESULTS: Early treatment response: the CR rates in E + CRT and CRT groups were 48.8% and 26.8%, respectively (χ2 = 4.20, P < .05). The ORR and DCR were not significantly different between the 2 groups. Long-term efficacy: there was no significant difference in the 1-year and 2-year PFS rates and OS rates between 2 groups. However, in patients with stage IIB, subgroup analyses revealed a significant difference in PFS between the 2 groups (P < .05). Prognostic factors: stage, Eastern Cooperative Oncology Group (ECOG) score, and tumor size were independent predictive factors for PFS, while ECOG score and tumor size were those of OS in patients with locally advanced cervical cancer. Safety: The incidence of grade III-IV myelosuppression was significantly lower in E + CRT group than in CRT group (P < .05). CONCLUSIONS: The combination of Endostar and concurrent CRT exhibited greater efficacy in treating locally advanced cervical cancer with no severe adverse reactions, when compared to simple CRT. It is expected that this approach will evolve into a new treatment alternative for patients with locally advanced cervical cancer.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

Multileaf Collimator Modeling and Commissioning for Complex Radiation Treatment Plans Using 2-Dimensional (2D) Diode Array MapCHECK2.

Purpose: This study aims to develop a data-collecting package ExpressMLC and investigate the applicability of MapCHECK2 for multileaf collimator (MLC) modeling and commissioning for complex radiation treatment plans. Materials and methods: The MLC model incorporates realistic parameters to account for sophisticated MLC features. A set of 8 single-beam plans, denoted by ExpressMLC, is created for the determination of parameters. For the commissioning of the MLC model, 4 intensity modulated radiation therapy (IMRT) plans specified by the AAPM TG 119 report were transferred to a computed tomography study of MapCHECK2, recalculated, and compared to measurements on a Varian accelerator. Both per-beam and composite-beam dose verification were conducted. Results: Through sufficient characterization of the MLC model, under 3%/2 mm and 2%/2 mm criteria, MapCHECK2 can be used to accurately verify per beam dose with gamma passing rate better than 90.9% and 89.3%, respectively, while the Gafchromic EBT3 films can achieve gamma passing rate better than 89.3% and 85.7%, respectively. Under the same criteria, MapCHECK2 can achieve composite beam dose verification with a gamma passing rate better than 95.9% and 90.3%, while the Gafchromic EBT3 films can achieve a gamma passing rate better than 96.1% and 91.8%; the p-value from the Mann Whitney test between gamma passing rates of the per beam dose verification using full MapCHECK2 package calibrated MLC model and film calibrated MLC model is .44 and .47, respectively; the p-value between those of the true composite beam dose verification is .62 and .36, respectively. Conclusion: It is confirmed that the 2-dimensional (2D) diode array MapCHECK2 can be used for data collection for MLC modeling with the combination of the ExpressMLC package of plans, whose doses are sufficient for the determination of MLC parameters. It could be a fitting alternative to films to boost the efficiency of MLC modeling and commissioning without sacrificing accuracy.

Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex shell for upconversion fluorescent and magnetic resonance dual-modality imaging.

Multi-modal imaging based on multifunctional nanoparticles is a promising alternative approach to improve the sensitivity of early cancer diagnosis. In this study, highly upconverting fluorescence and strong relaxivity rare-earth nanoparticles coated with paramagnetic lanthanide complex shells and polyethylene glycol (PEGylated UCNPs@DTPA-Gd(3+)) are synthesized as dual-modality imaging contrast agents (CAs) for upconverting fluorescent and magnetic resonance dual-modality imaging. PEGylated UCNPs@DTPA-Gd(3+) with sizes in the range of 32-86 nm are colloidally stable. They exhibit higher longitudinal relaxivity and transverse relaxivity in water (r1 and r2 values are 7.4 and 27.8 s(-1) per mM Gd(3+), respectively) than does commercial Gd-DTPA (r1 and r2 values of 3.7 and 4.6 s(-1) per mM Gd(3+), respectively). They are found to be biocompatible. In vitro cancer cell imaging shows good imaging contrast of PEGylated UCNPs@DTPA-Gd(3+). In vivo upconversion fluorescent imaging and T1-weighted MRI show excellent enhancement of both fluorescent and MR signals in the livers of mice administered PEGylated UCNPs@DTPA-Gd(3+). All the experimental results indicate that the synthesized PEGylated UCNPs@DTPA-Gd(3+) present great potential for biomedical upconversion of fluorescent and magnetic resonance dual-modality imaging applications.