Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study.

Background: Clinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis. Methods: Data of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups' clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients' prognosis. Results: There was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70-0.87; CSS: AUC 0.74-0.89). Conclusion: Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

Surufatinib combined with photodynamic therapy induces ferroptosis to inhibit cholangiocarcinoma in vitro and in tumor models.

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

Adaptive tracking control for nonlinear systems with uncertain control gains and its application to a TCP/AQM network.

This paper is concerned with the adaptive tracking control problem for nonlinear systems with virtual control coefficients including known and unknown items. The known items are employed for controller design directly, such that more information is utilized to achieve better performance. To deal with the unknown items, a novel real control law is firstly constructed by introducing an auxiliary system. The proposed controller is designed and applied to an uncertain TCP/AQM network system, which guarantees the practical boundedness of all the signals in the closed-loop system. Finally, the effectiveness and practicability of the developed control strategy are validated by simulation results.

Prognosis prediction and comparison between pancreatic signet ring cell carcinoma and pancreatic duct adenocarcinoma: a retrospective observational study.

Background: Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale epidemiological and prognostic analyses, the outcomes of PSRCC patients varies greatly in the absence of recognized first-line treatment strategies. This study aimed to compare the clinical features, treatment, and prognosis of PSRCC and pancreatic ductal cell carcinoma (PDAC), the most common subtype of pancreatic cancer, and to establish predictive models for these subtypes. Methods: The data on PSRCC and PDAC patients from 1998 to 2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Thereafter, the clinical, demographic, and treatment characteristics of the two groups and the differences and influencing factors of the two groups were evaluated by propensity score matching (PSM), Kaplan-Meier survival curves, Cox risk regression analyses, and least absolute shrinkage and selection operator (LASSO) analysis. Next, prognosis models were constructed and validated by KM and ROC analysis. Finally, a nomogram was constructed, based on the results of these analyses, to predict survival outcomes of PSRCC and PDAC patients. Results: A total of 84,789 patients (432 PSRCC and 84357 PDAC patients) were included in this study. The results of the study revealed that, compared to the PDAC patients, PSRCC patients were more likely to be male, aged between 58-72 years, have larger tumor masses, and less likely to undergo chemotherapy. Before PSM, the overall survival and cancer-specific survival of the PSRCC group were significantly lower than those PDAC group, but there was no difference in the prognosis of the two groups after PSM. Additionally, lymph node ratio (LNR), log odds of positive lymph node (LODDS), tumor size, age, T-stage, marital status, and summary stage were found to be independent prognostic factors for PSRCC. Lastly, the prediction model and nomogram based on these prognostic factors could accurately predict the survival rate of the patients in SEER datasets and external validation datasets. Conclusion: The prognosis of PSRCC and PDAC patients is similar under the same conditions; however, PSRCC patients may have more difficulty in receiving better treatment, thus resulting in their poor prognosis.

Binding Mechanism of Inhibitors to Heat Shock Protein 90 Investigated by Multiple Independent Molecular Dynamics Simulations and Prediction of Binding Free Energy.

The heat shock protein (HSP90) has been an import target of drug design in the treatment of human disease. An exploration of the conformational changes in HSP90 can provide useful information for the development of efficient inhibitors targeting HSP90. In this work, multiple independent all-atom molecular dynamics (AAMD) simulations followed by calculations of the molecular mechanics generalized Born surface area (MM-GBSA) were performed to explore the binding mechanism of three inhibitors (W8Y, W8V, and W8S) to HSP90. The dynamics analyses verified that the presence of inhibitors impacts the structural flexibility, correlated movements, and dynamics behavior of HSP90. The results of the MM-GBSA calculations suggest that the selection of GB models and empirical parameters has important influences on the predicted results and verify that van der Waals interactions are the main forces that determine inhibitor-HSP90 binding. The contributions of separate residues to the inhibitor-HSP90 binding process indicate that hydrogen-bonding interactions (HBIs) and hydrophobic interactions play important roles in HSP90-inhibitor identifications. Moreover, residues L34, N37, D40, A41, D79, I82, G83, M84, F124, and T171 are recognized as hot spots of inhibitor-HSP90 binding and provide significant target sites of for the design of drugs related to HSP90. This study aims to contribute to the development of efficient inhibitors that target HSP90 by providing an energy-based and theoretical foundation.

Intersection of nanomaterials and organoids technology in biomedicine.

Organoids are stem cell-derived, self-organizing, 3D structures. Compared to the conventional 2D cell culture method, 3D cultured organoids contain a variety of cell types that can form functional "micro-organs" and can be used to simulate the occurrence process and physiological pathological state of organ tissues more effectively. Nanomaterials (NMs) are becoming indispensable in the development of novel organoids. Understanding the application of nanomaterials in organoid construction can, therefore, provide researchers with ideas for the development of novel organoids. Here, we discuss the application status of NMs in various organoid culture systems and the research direction of NMs combined with organoids in the biomedical field.

Comprehensive Pan-Cancer Analysis of MTF2 Effects on Human Tumors.

Understanding oncogenic processes and underlying mechanisms to advance research into human tumors is critical for effective treatment. Studies have shown that Metal regulatory transcription factor 2（MTF2) drives malignant progression in liver cancer and glioma. However, no systematic pan-cancer analysis of MTF2 has been performed. Here, we use University of California Santa Cruz, Cancer Genome Atlas , Genotype-Tissue Expression data, Tumor Immune Estimation Resource, and Clinical Proteomic Tumor Analysis Consortium bioinformatics tools to explore differential expression of MTF2 across different tumor types. MTF2 was found to be highly expressed in the cancer lines that were available through the respective databases included in the study, and overexpression of MTF2 may lead to a poor prognosis in tumor patients such as glioblastoma multiforme, brain lower grade glioma, KIPAN, LIHC, adrenocortical carcinoma, etc. We also validated MTF2 mutations in cancer, compared MTF2 methylation levels in normal and primary tumor tissues, analyzed the association of MTF2 with the immune microenvironment, and validated the functional role of MTF2 in glioma U87 and U251 and breast cancer MDA-MB-231 cell lines by cytometry. This also indicates that MTF2 has a promising application prospect in cancer treatment.

Identification of immune related gene signature for predicting prognosis of cholangiocarcinoma patients.

Objective: To identify the gene subtypes related to immune cells of cholangiocarcinoma and construct an immune score model to predict the immunotherapy efficacy and prognosis for cholangiocarcinoma. Methods: Based on principal component analysis (PCA) algorithm, The Cancer Genome Atlas (TCGA)-cholangiocarcinoma, GSE107943 and E-MTAB-6389 datasets were combined as Joint data. Immune genes were downloaded from ImmPort. Univariate Cox survival analysis filtered prognostically associated immune genes, which would identify immune-related subtypes of cholangiocarcinoma. Least absolute shrinkage and selection operator (LASSO) further screened immune genes with prognosis values, and tumor immune score was calculated for patients with cholangiocarcinoma after the combination of the three datasets. Kaplan-Meier curve analysis determined the optimal cut-off value, which was applied for dividing cholangiocarcinoma patients into low and high immune score group. To explore the differences in tumor microenvironment and immunotherapy between immune cell-related subtypes and immune score groups of cholangiocarcinoma. Results: 34 prognostic immune genes and three immunocell-related subtypes with statistically significant prognosis (IC1, IC2 and IC3) were identified. Among them, IC1 and IC3 showed higher immune cell infiltration, and IC3 may be more suitable for immunotherapy and chemotherapy. 10 immune genes with prognostic significance were screened by LASSO regression analysis, and a tumor immune score model was constructed. Kaplan-Meier (KM) and receiver operating characteristic (ROC) analysis showed that RiskScore had excellent prognostic prediction ability. Immunohistochemical analysis showed that 6 gene (NLRX1, AKT1, CSRP1, LEP, MUC4 and SEMA4B) of 10 genes were abnormal expressions between cancer and paracancer tissue. Immune cells infiltration in high immune score group was generally increased, and it was more suitable for chemotherapy. In GSE112366-Crohn's disease dataset, 6 of 10 immune genes had expression differences between Crohn's disease and healthy control. The area under ROC obtained 0.671 based on 10-immune gene signature. Moreover, the model had a sound performance in Crohn's disease. Conclusion: The prediction of tumor immune score model in predicting immune microenvironment, immunotherapy and chemotherapy in patients with cholangiocarcinoma has shown its potential for indicating the effect of immunotherapy on patients with cholangiocarcinoma.

Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis.

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and the limited penetration depth of light in tissues, the extensive clinical application of PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based PDT as a promising cancer treatment to overcome cancer resistance in combination with ferroptosis. The treatment efficiency of Cu-Cy-mediated microwave dynamic therapy (MWDT) tested on HCT15 colorectal cancer (CRC) cells via cell titer-blue cell viability assay and live/dead assay reveal that Cu-Cy upon MW irradiation can effectively destroy HCT15 CRC cells with average IC-50 values of 20 µg/mL. The cytotoxicity of Cu-Cy to tumor cells after MW stimulation can be alleviated by ferroptosis inhibitor. Furthermore, Cu-Cy mediated MWDT could deplete glutathione peroxide 4 (GPX4) and enhance lipid peroxides (LPO) and malondialdehyde (MDA). Our findings demonstrate that MW-activated Cu-Cy killed CRC cells by inducing ferroptosis. The superior in vivo antitumor efficacy of the Cu-Cy was corroborated by a HCT15 tumor-bearing mice model. Immunohistochemical experiments showed that the GPX4 expression level in Cu-Cy + MW group was significantly lower than that in other groups. Overall, these findings demonstrate that Cu-Cy nanoparticles have a safe and promising clinical application prospect in MWDT for deep-seated tumors and effectively inhibit tumor cell proliferation by inducing ferroptosis, which provides a potential solution for cancer resistance.

Recent advances of NEAT1-miRNA interactions in cancer.

With high incidence rate, cancer is the main cause of death in humans. Non-coding RNAs, as novel master regulators, especially long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play important roles in the regulation of tumorigenesis. lncRNA NEAT1 has recently gained much attention, as it is dysregulated in a broad spectrum of cancers, where it acts as either an oncogene or a tumor suppressor gene. Accumulating evidence shows that NEAT1 is correlated with the process of carcinogenesis, including proliferation, invasion, survival, drug resistance, and metastasis. NEAT1 is considered to be a biomarker and a novel therapeutic target for the diagnosis and prognosis of different cancer types. The mechanisms by which NEAT1 plays a critical role in cancers are mainly via interactions with miRNAs. NEAT1-miRNA regulatory networks play significant roles in tumorigenesis, which has attracted much attention from researchers around the world. In this review, we summarize the interaction of NEAT1 with miRNAs in the regulation of protein-coding genes in cancer. A better understanding of the NEAT1-miRNA interactions in cancer will help develop new diagnostic biomarkers and therapeutic approaches.

Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy.

Autophagy related gene 101 (ATG101) plays a significant role in the occurrence and development of tumours by responding to stress. Our research aims to illustrate the correlation between the expression of ATG101 and tumor prognosis and its potential role and mechanism in tumor immunity and photodynamic therapy (PDT). First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, Kaplan-Meier curves was applied in cholangiocarcinoma (CHOL) and liver hepatocellular carcinoma (LIHC) datasets for survival analysis. Next, the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints was analysed. Besides, the relationship between the expression of ATG101 and methyltransferase. GSEA was used to study the function and the related transcript factors of ATG101 in CHOL and LIHC. The effect of PDT on ATG101 was verified by microarray, qPCR and western blot. Then the effect of ATG101 and its regulatory factors on apoptosis were verified by siRNA, lentivirus transfection and Chip-qPCR. Comprehensive analysis showed that ATG101 was overexpressed in different tumours. Kaplan-Meier curves found that ATG101 was associated with poor prognosis in tumours (including CHOL and LIHC). We found that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in CHOL and LIHC. Subsequent validation tests confirmed that the up-regulated ATG101 after PDT treatment is not conducive to the occurrence of apoptosis of cholangiocarcinoma cells. The high expression of ATG101 may be induced by the early stress gene EGR2. Our study highlights the significance of ATG101 in the study of tumour immunity and photodynamic therapy from a pan-cancer perspective.

Colorectal liver metastasis: molecular mechanism and interventional therapy.

Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

Degradation of tetracycline by FeNi-LDH/Ti3C2 photo-Fenton system in water: From performance to mechanism.

Recently, photo-Fenton technology has been widely used to degrade tetracycline (TC) because of its great efficiency and wide application range. Herein, Fe-Ni layered double hydroxides (FeNi-LDH)/Ti3C2 photo-Fenton system was constructed in this study. The results showed the introduction of Ti3C2 solved some problems of FeNi-LDH such as poor conductivity, easy aggregation, and high recombination rate of photoelectron. Benefiting from these advantages, FeNi-LDH/Ti3C2 exhibited excellent TC removal rate of 94.7% while pure FeNi-LDH was only 54%. Besides, FeNi-LDH/Ti3C2 possessed strong pH tolerance (2-11) and the removal efficiency was still up to 82% after the four-cycle experiment. Furthermore, the quenching experiments revealed the reaction mechanism, where ∙OH and ·O2- were the primary active radicals for degrading TC. Last, the results of the simulated wastewater treatment and the inorganic ion interference tests showed that FeNi-LDH/Ti3C2 possessed practical application potential. In brief, this study shows that FeNi-LDH/Ti3C2 can offer a certain theoretical basis for the actual development of hydrotalcite in heterogeneous photo-Fenton systems.

Radiotherapy inhibits neointimal hyperplasia after artificial vascular replacement through Skp2/P27kip1.

We aimed to establish an animal model of abdominal aortic vascular replacement in mongrel dogs to investigate the effect of extracorporeal radiotherapy on the intima. Twenty healthy mongrel dogs were randomly divided into four groups: 5-week control group, 5-week radiotherapy group, 10-week control group and 10-week radiotherapy group. We first performed an artificial vascular replacement of the abdominal aortic segment. The radiotherapy group received external radiotherapy with a dose of 7 Gy for 4 days. The thickness of neointimal hyperplasia, immunoreactivity and expression of proliferation-related factors were detected by hematoxylin and eosin (HE) staining, immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR )and western blotting at 5 and 10 weeks after the reconstruction. The results showed that the intimal thickness of the artificial blood vessel in the 5- and 10-week radiotherapy groups was thinner than that in the control groups by HE staining. The immunoreactivity and expression levels of Skp2, c-Myc and CyclinE1 were significantly decreased in the radiotherapy groups than those in control groups by immunohistochemistry, qRT-PCR and western blotting. On the contrary, immunoreactivity and expression levels of P27kip1 were increased. In conclusion, we discovered that postoperative external radiotherapy significantly decreases the intimal hyperplasia of artificial blood vessels by regulating c-Myc-Skp2-P27-CyclinE1 network.

A novel prognostic gene set for colon adenocarcinoma relative to the tumor microenvironment, chemotherapy, and immune therapy.

Background: Colon adenocarcinoma (COAD) is a common aggressive malignant tumor. Heterogeneity in tumorigenesis and therapy response leads to an unsatisfactory overall survival of colon adenocarcinoma patients. Our study aimed to identify tools for a better prediction of colon adenocarcinoma prognosis, bolstering the development of a better personalized treatment and management. Method: We used the least absolute shrinkage and selection operator (LASSO) Cox model to analyze the prognosis-related gene datasets from the Gene Expression Omnibus (GEO) database and verified them using The Cancer Genome Atlas (TCGA) database. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to evaluate the predictive ability of the risk score model. Gene Set Enrichment Analysis (GSEA) was used to identify the significantly enriched and depleted biological processes. The tumor immune dysfunction and exclusion (TIDE) algorithm was taken to explore the relationship between the risk score and immunotherapy. The observations collectively helped us construct a nomogram to predict prognosis. Finally, the correlation between drug sensitivity and prognostic gene sets was conducted based on the Cancer Therapeutics Response Portal (CTRP) analyses. Results: We constructed a scoring model to assess the significance of the prognosis risk-related gene signatures, which was relative to common tumor characteristics and tumor mutational burdens. Patients with a high-risk score had higher tumor stage and poor prognosis (p< 0.05). Moreover, the expressions of these genes were in correlation with changes in the tumor microenvironment (TME). The risk score is an independent prognostic factor for COAD (p< 0.05). The accuracy of the novel nomogram model with a risk score and TNM-stage prediction prognosis in the predicting prognosis was higher than that of the TNM stage. Further analysis showed that a high-risk score was associated with tumor immune rejection. Patients with a low-risk score have a better prognosis with chemotherapy than those with a high-risk score. Compared to patients in the high-risk group, patients in the low-risk group had a significant survival advantage after receiving chemotherapy. In addition, the prognostic gene sets aid the assessment of drug sensitivity. Conclusion: This study establishes a new prognostic model to better predict the clinical outcome and TME characteristics of colon adenocarcinoma. We believe, our model also serves as a useful clinical tool to strengthen the functioning of chemotherapy, immunotherapy, and targeted drugs.

A Novel Ferroptosis-Related 4-Gene Prognostic Signature for Cholangiocarcinoma and Photodynamic Therapy.

Cholangiocarcinoma is the second most common malignant tumor in the hepatobiliary system. Compared with data on hepatocellular carcinoma, fewer public data and prognostic-related studies on cholangiocarcinoma are available, and effective prognostic prediction methods for cholangiocarcinoma are lacking. In recent years, ferroptosis has become an important subject of tumor research. Some studies have indicated that ferroptosis plays an important role in hepatobiliary cancers. However, the prediction of the prognostic effect of ferroptosis in patients with cholangiocarcinoma has not been reported. In addition, many reports have described the ability of photodynamic therapy (PDT), a potential therapy for cholangiocarcinoma, to regulate ferroptosis by generating reactive oxygen species (ROS). By constructing ferroptosis scores, the prognoses of patients with cholangiocarcinoma can be effectively predicted, and potential gene targets can be discovered to further enhance the efficacy of PDT. In this study, gene expression profiles and clinical information (TCGA, E-MTAB-6389, and GSE107943) of patients with cholangiocarcinoma were collected and divided into training sets and validation sets. Then, a model of the ferroptosis gene signature was constructed using least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. Furthermore, through the analysis of RNA-seq data after PDT treatment of cholangiocarcinoma, PDT-sensitive genes were obtained and verified by immunohistochemistry staining and Western blot. The results of this study provide new insight for predicting the prognosis of cholangiocarcinoma and screening target genes that enhance the efficacy of PDT.

Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT.

Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.

Supplementation With Dexmedetomidine for Transsphenoidal Resection of Pituitary Adenoma: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The effect of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexmedetomidine supplementation on hemodynamic stability for transsphenoidal resection of pituitary adenoma. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2020 for randomized controlled trials assessing the effect of dexmedetomidine supplementation on transsphenoidal resection of pituitary adenoma. RESULTS: Four randomized controlled trials involving 160 patients were included in the meta-analysis. Overall, compared with the control group for transsphenoidal resection of pituitary adenoma, dexmedetomidine supplementation resulted in significantly reduced mean arterial pressure at 30 minutes [mean difference (MD), -26.62; 95% confidence interval (CI), -36.71 to -16.53; P < 0.00001], heart rate at 30 minutes (MD, -16.50; 95% CI, -32.48 to -0.53; P = 0.04), blood loss (MD, -112.57; 95% CI, -165.12 to -60.01; P < 0.0001), and fentanyl (MD, -154.13; 95% CI, -303.97 to -4.29; P = 0.04), but demonstrated similar incidence of nausea and vomiting (odds ratio, 0.37; 95% CI, 0.13-1.03; P = 0.06), and hypotension (odds ratio, 2.11; 95% CI, 0.49-9.22; P = 0.32). CONCLUSIONS: Dexmedetomidine supplementation was effective in improving hemodynamic stability for transsphenoidal resection of pituitary adenoma.

Novel circular RNA 2960 contributes to secondary damage of spinal cord injury by sponging miRNA-124.

Recent studies have shown that circular RNAs (circRNAs) are involved in many human diseases, but their roles in secondary damage after spinal cord injury (SCI) remain unclear. In the current study circRNA sequencing was performed in the damaged tissues of SCI rats on the seventh day after injury, and related molecular mechanisms were investigated. Quantitative PCR validations of molecules that exhibited significantly altered expression in SCI mice were performed. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to assess differentially expressed circRNAs. A novel circRNA-2960 was the most significantly upregulated in the SCI group. It could downregulate its target molecule miRNA-124, then exacerbate the inflammatory response and induce apoptosis at the lesion site. Disrupting circRNA-2960 expression promoted recovery of tissues affected by secondary SCI damage. The results of the present study may provide new insight into the mechanisms of secondary injury in SCI, and a new molecular marker for the diagnosis and treatment of SCI.

Novel Span-PEG Multifunctional Ultrasound Contrast Agent Based on CNTs as a Magnetic Targeting Factor and a Drug Carrier.

Based on the targeting of ferroferric oxide (Fe3O4) and the drug-loading property of carbon nanotubes (CNTs), a novel Span-PEG-composited Fe3O4-CNTs-DOX multifunctional ultrasound contrast agent was designed and applied to tumor lesions. In situ liquid phase synthesis was employed to prepare the Fe3O4-CNTs magnetic targeting complex, and the physical method was used to obtain the Fe3O4-CNTs-DOX complex by loading doxorubicin (DOX) onto Fe3O4-CNTs. The targeted drug-loading complex Fe3O4-CNTs-DOX was combined with the membrane material of Span-PEG by the acoustic vibration cavitation method. The maximum tolerance for Span-PEG-composited Fe3O4-CNTs-DOX microbubbles was 450 times higher, which has good safety. The loading rate of DOX in the obtained composite microbubbles was 17.02%. The proliferation inhibition rate of Span-PEG-composited Fe3O4-CNTs-DOX microbubbles on liver cancer SMMC-7721 cells reached 48.3%. Span-PEG-composited Fe3O4-CNTs-DOX microbubbles could significantly enhance ultrasonic imaging and enrich at a specific location under an external magnetic field, and the extended imaging time could ensure the effective observation and diagnosis of lesions.