Ethanolic extract of Arctium lappa leaves alleviates cerebral ischemia reperfusion-induced inflammatory injury via HDAC9-mediated NF-κB pathway.

BACKGROUND: Ischemic stroke (IS) is a major cause of mortality and disability worldwide. Inflammatory response is crucial in the pathogenesis of tissue injury in cerebral infarction. Arctium lappa leaves are traditionally used to treat IS. PURPOSES: To investigate the neuroprotective effects and molecular mechanisms of the ethanolic extract of A. lappa leaves (ALLEE) on cerebral ischemia-reperfusion (CIR). METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) rats and an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model were used to evaluate ALLEE pharmacodynamics. Various methods, including neurological function, 2,3,5-triphenyltetrazolium chloride, hematoxylin and eosin, and Nissl, enzyme-linked immunosorbent, and TdT-mediated dUTP nick-end labeling assays, were used to analyze the neuroprotective effects of ALLEE in vitro and in vivo. The major chemical components and potential target genes of ALLEE were screened using network pharmacology. Molecular docking, western blotting, and immunofluorescence analyses were performed to confirm the effectiveness of the targets in related pathways. RESULTS: ALLEE exerted potent effects on the MCAO/R model by decreasing the neurological scores, infarct volumes, and pathological features (p < 0.01). Furthermore, network pharmacology results revealed that the treatment of IS with ALLEE involved the regulation of various inflammatory pathways, such as the tumor necrosis factor (TNF) and chemokine signaling pathways. ALLEE also played key roles in targeting key molecules, including nuclear factor (NF)-κBIA, NF-κB1, interleukin (IL)-6, TNF-α and IL1ß, and regulating the histone deacetylase (HDAC)-9-mediated signaling pathway. In vivo and in vitro analyses revealed that ALLEE significantly regulated the NF-κB pathway, promoted the phosphorylation activation of NF-κB P65, IκB and IKK (p < 0.01 or p < 0.05), and decreased the expression levels of the inflammatory factors, IL-1ß, IL-6 and TNF-α (p < 0.01). Moreover, ALLEE significantly decreased the expression of HDAC9 (p < 0.01) that is associated with inflammatory responses. However, HDAC9 overexpression partially reversed the neuroprotective effects of ALLEE and its suppressive effects on inflammation and phosphorylation of NF-κB (p < 0.01). CONCLUSIONS: In conclusion, our results revealed that ALLEE ameliorates MCAO/R-induced experimental CIR by modulating inflammatory responses via the inhibition of HDAC9-mediated NF-κB pathway.

RUNX1 promotes proliferation and migration in non-small cell lung cancer cell lines via the mTOR pathway.

RUNX1, a member of the RUNX family of metazoan transcription factors, participates in the regulation of differentiation, proliferation, and other processes involved in growth and development. It also functions in the occurrence and development of tumors. However, the role and mechanism of action of RUNX1 in non-small cell lung cancer (NSCLC) are not yet clear. We used a bioinformatics approach as well as in vitro and in vivo assays to evaluate the role of RUNX1 in NSCLC as the molecular mechanisms underlying its effects. Using the TCGA, GEO, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier databases, we screened the differentially expressed genes (DEGs) and found that RUNX1 was highly expressed in lung cancer and was associated with a poor prognosis. Immunohistochemical staining based on tissue chips from 110 samples showed that the expression of RUNX1 in lung cancer tissues was higher than that in adjacent normal tissues and was positively correlated with lymph node metastasis and TNM staging. In vitro experiments, we found that RUNX1 overexpression promoted cell proliferation and migration functions and affected downstream functional proteins by regulating the activity of the mTOR pathway, as confirmed by an analysis using the mTOR pathway inhibitor rapamycin. In addition, RUNX1 affected PD-L1 expression via the mTOR pathway. These results indicate that RUNX1 is a potential therapeutic target for NSCLC.

Atypical thymic carcinoid tumor with ectopic ACTH syndrome in a 33-year-old male patient: A rare case report and literature review.

RATIONALE: Atypical thymic carcinoid tumor is an exceedingly rare thymic neuroendocrine tumor derived from the cells of neuroendocrine system. Misdiagnosis or delayed diagnosis may result in disease progression to advanced stages and eventually leads to a poor prognosis. It is therefore necessary to make a correct diagnosis and provide an adequate treatment. PATIENT CONCERNS: A 33-year-old Chinese male presented with numbness in bilateral lower extremities and general fatigue for a month. Chest computed tomography revealed a superior anterior mediastinal mass. Thymoma was initially considered, given the location of the mass and radiographic presentation. DIAGNOSIS: Microscopic findings showed that the tumor cells are arranged in pseudoepitheliomatous growth or irregular nested growth pattern in a background of fibroconnective tissue, with focal infiltration into adipose tissue. The chrysanthemum-like structure or beam-like structure seen often in typical carcinoid tumor was not identified in this case. The tumor cells are spindled or oval, with focal active mitosis. The immunohistochemical staining showed strong positivity for CD56, CgA and Syn, positivity for CK, ACTH, and TTF-1, negativity for Vimentin, and ki67 labeled proliferation index was up to 10% in focal areas. According to the radiological and pathological findings, the diagnosis of atypical thymic carcinoid was made. INTERVENTIONS: The patient underwent surgical resection of the mass. OUTCOME: No recurrence or metastasis was identified during the follow up. LESSONS: Because of its low incidencen, onspecific clinical symptoms, tissue location, and radiological findings, atypical thymic carcinoid tumor may sometimes be misdiagnosed as thymoma. Attention should be paid to avoid misdiagnosis.

TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion.

Diffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, and was significantly correlated with malignant phenotypes and a poor prognosis. In vitro and in vivo experimental studies revealed that TRIM56 promoted the migration and invasion of glioma cells. Mechanistically, TRIM56 was transcriptionally regulated by SP1 and promoted the K48-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with it, which in turn promoted CDC42 activation. This mechanism was confirmed to mediate glioma migration and invasion. In conclusion, our study provides insights into the mechanisms through which TRIM56 promotes glioma motility, i.e., by regulating IQGAP1 ubiquitination to promote CDC42 activation, which might be clinically targeted for the treatment of glioma.

Highly Stretchable, Self-Adhesive, Antidrying Ionic Conductive Organohydrogels for Strain Sensors.

As flexible wearable devices, hydrogel sensors have attracted extensive attention in the field of soft electronics. However, the application or long-term stability of conventional hydrogels at extreme temperatures remains a challenge due to the presence of water. Antifreezing and antidrying ionic conductive organohydrogels were prepared using cellulose nanocrystals and gelatin as raw materials, and the hydrogels were prepared in a water/glycerol binary solvent by a one-pot method. The prepared hydrogels were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The mechanical properties, electrical conductivity, and sensing properties of the hydrogels were studied by means of a universal material testing machine and LCR digital bridge. The results show that the ionic conductive hydrogel exhibits high stretchability (elongation at break, 584.35%) and firmness (up to 0.16 MPa). As the binary solvent easily forms strong hydrogen bonds with water molecules, experiments show that the organohydrogels exhibit excellent freezing and drying (7 days). The organohydrogels maintain conductivity and stable sensitivity at a temperature range (-50 °C-50 °C) and after long-term storage (7 days). Moreover, the organohydrogel-based wearable sensors with a gauge factor of 6.47 (strain, 0-400%) could detect human motions. Therefore, multifunctional organohydrogel wearable sensors with antifreezing and antidrying properties have promising potential for human body monitoring under a broad range of environmental conditions.

A Facile One-Pot Preparation and Properties of Nanocellulose-Reinforced Ionic Conductive Hydrogels.

Nanocellulose-reinforced ionic conductive hydrogels were prepared using cellulose nanofiber (CNF) and polyvinyl alcohol (PVA) as raw materials, and the hydrogels were prepared in a dimethyl sulfoxide (DMSO)/water binary solvent by a one-pot method. The prepared hydrogels were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The mechanical properties, electrical conductivity, and sensing properties of the hydrogels were studied by means of a universal material testing machine and LCR digital bridge. The results show that the ionic conductive hydrogel exhibits high stretchability (elongation at break, 206%) and firmness (up to 335 KPa). The tensile fracture test shows that the hydrogel has good properties in terms of tensile strength, toughness, and elasticity. The hydrogel as a conductor medium is assembled into a self-powered strain sensor and the open-circuit voltage can reach 0.830 V. It shows good sensitivity in the bend sensing testing, indicating that the hydrogel has good sensing performance. The water retention and anti-freezing performance experiments show that the addition of dimethyl sulfoxide solvents can effectively improve the anti-freezing and water retention properties of hydrogels.

Role of MicroRNA-214 in Dishevelled1-Modulated ß-catenin Signalling in Non-Small Cell Lung Cancer Progression.

Background: The mortality of patients with non-small cell lung cancer (NSCLC) is rather high. This is largely because of the lack of specific targets and understanding of the molecular mechanism for early diagnosis. Dishevelled (Dvl) dysregulation leads to malignant progression. We confirmed that Dvl1 expression is associated with a poor prognosis of patients with NSCLC. However, how Dvl1 transmits signals through the Wnt/ß-catenin pathway remains unknown. Methods: In this study, the expression levels of Dvl1 and ß-catenin in resected NSCLC samples were immunohistochemically analysed. Dvl1 cDNA and small interfering RNA against ß-catenin were transfected into NSCLC cells, and their effects on canonical Wnt signalling and biological behaviour of NSCLC cells were analysed. Using bioinformatics analyses, an interaction between microRNA (miR)-214 and ß-catenin was identified; miR-214 expression was determined in NSCLC tissues using quantitative real-time polymerase chain reaction. An exogenous miR-214 (mimic) was used to analyse the biological behaviour of NSCLC cells and the effect of Dvl1 on canonical Wnt activation. Results: Dvl1 overexpression in NSCLC tissues as well as Dvl1 and ß-catenin nuclear coexpression were significantly associated with poor prognosis of NSCLC (P < 0.05). Additionally, Dvl1 promoted Wnt/ß-catenin signalling to enhance the malignant phenotype of NSCLC cells. Moreover, miR-214 directly targeted the 3' untranslated region of ß-catenin to inhibit the activation of canonical Wnt signalling induced by Dvl1. Conclusions: Our results suggest that Dvl1 is a potential therapeutic target for NSCLC and that miR-214 plays an inhibitory role in Dvl1-mediated activation of Wnt/ß-catenin signalling in NSCLC cells, which could affect NSCLC progression.

Endometrioid adenofibroma of ovary: A case report and review of literature.

RATIONALE: Endometrioid adenofibroma is a benign epithelial neoplasm of the ovary, most of which are often unilateral. The symptoms of endometrioid adenofibroma are often nonspecific and misleading. Therefore, a full understanding of the characteristics, diagnosis, and treatment methods of this disease is of great importance. In this study, we report a 34-year-old woman who was found with an unidentified mass on the right ovary during the physical examination 3 years ago with nosymptoms or signs. PATIENT CONCERNS: A 34-year-old Chinese female was found with an unidentified 6 cm mass on the right ovary for 3 years that presented with no symptoms or signs. DIAGNOSIS: Pelvic ultrasound revealed a 6 cm cystic solid mixed mass on the right ovary. Through histological and immunohistochemical examinations, the tumor mass was finally diagnosed as endometrioid adenofibroma of ovary. INTERVENTIONS: To confirm the diagnosis, the ovarian tumor was laparoscopically resected. OUTCOMES: The patient returned to hospital after 3 months with no recurrence or postoperative complications. LESSONS: Endometrioid adenofibroma is a benign epithelial neoplasm of the ovary. Complete surgical resection is required and rare cases can recur. Postsurgical pathologic and immunohistochemical testing can confirm a diagnosis of endometrioid adenofibroma. It is important to understand of the key points of differential diagnosis of the disease due to the different prognosis and clinical treatment.

Arctium lappa leaves based on network pharmacology and experimental validation attenuate atherosclerosis by targeting the AMPK-mediated PPARG/LXRα pathway.

Arctium lappa (A. lappa) leaves are widely used in various traditional Chinese herbal formulae to ameliorate atherosclerosis (AS) and its complications such as stroke; however, there is no literature reporting the anti-atherosclerotic effect and mechanism of A. lappa leaves thus far. In the present study, we used network pharmacology and molecular docking approaches to examine the protective effect and potential mechanism of A. lappa leaves against AS in vivo and in vitro. From the network pharmacology, PPARG, HMGCR and SREBF2 were identified as the core targets of A. lappa leaves against AS. Further enrichment analyses of GO and KEGG pathways suggested that A. lappa leaves might play an anti-AS role by regulating metabolic processes and PPAR signalling pathways. The results of molecular docking experiment revealed that the major components of A. lappa leaves interacted with cholesterol efflux-regulating core proteins (PPARG, LXRα, ABCA1, and ABCG1), AMPK and SIRT1. Both in vivo and in vitro experimental results demonstrated that treatment with A. lappa leaves significantly lowered TC and LDL-C, increased HDL-C, and reduced cholesterol accumulation in the liver and aorta of the AS rat model and the foam cell model. Importantly, both in vivo and in vitro experimental results demonstrated that A. lappa leaves regulate the activity of the PPARG/LXRα signalling and AMPK/SIRT1 signalling pathways. Moreover, after treatment with the AMPK inhibitor Compound C in vitro, the improvement induced by A. lappa leaves was significantly reversed. In conclusion, A. lappa leaves attenuated AS-induced cholesterol accumulation by targeting the AMPK-mediated PPARG/LXRα pathway and promoting cholesterol efflux.

Intra-tumoral angiogenesis correlates with immune features and prognosis in glioma.

Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.

Preparation and properties of cellulose nanocrystal-based ion-conductive hydrogels.

Ion-conductive hydrogels were prepared by a simple one-pot method based on cellulose nanocrystals (CNC) and polyvinyl alcohol (PVA). PVA-CNC hydrogels were prepared with different contents of CNC and Al3+ ions to enhance the performance of ion-conductive hydrogels. The samples were characterized by Fourier transform infrared spectroscopy, universal testing machine, LCR digital bridge and scanning electron microscopy analyses. The results show that DMSO solvent can enhance the anti-freezing and moisture retention property of the polyvinyl alcohol hydrogel. With the increase of CNC content in the hydrogels, their mechanical properties are also improved. When the CNC concentration is 0.2 wt%, the maximum tensile strength and elongation at break are 750 KPa and 410.47%, respectively. Compared to the hydrogel without CNC, the tensile strength of the hydrogel with 0.2 wt% CNC was increased to 733% and elongation at break was increased to 236%. However, the mechanical properties of the hydrogel will decrease when the CNC content increases to 0.25 wt%. When the hydrogel is stretched, the relative resistance of the hydrogel increases with the increase of tensile deformation. The hydrogels can also be assembled to form self-powered batteries with a voltage of 0.808 V. This indicates that the hydrogels have potential application value in flexible sensors.

Mechanism by which Eucommia ulmoides leaves Regulate Nonalcoholic fatty liver disease based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides (E. ulmoides) leaves are included in the Chinese Pharmacopoeia, and are traditionally used to treat hypertension, obesity, diabetes, and other diseases. Numerous pharmacological studies have shown that E. ulmoides has a good effect on lowering blood lipids and can improve obesity and nonalcoholic fatty liver. AIM: To study the mechanism of E. ulmoides leaves in regulating nonalcoholic fatty liver disease by combining prediction and validation. METHODS: Using network pharmacology, and molecular docking to predict E. ulmoides in regulating the action mechanism and potential active ingredients of nonalcoholic fatty liver, large hole adsorption resin enrichment active sites, in vitro experiments were performed to verify its fat-lowering effect and mechanism. RESULTS: The major components of E. ulmoides leaves exhibited good combination with lipid metabolism-regulating core proteins, particularly flavonoids. EUL 50 significantly reduced lipid accumulation, and increased PPARγ. Compared with the control group, the autophagy level increased after the administration of EUL 50. PPARγ decreased significantly after the addition of chloroquine (CQ, autophagy inhibitor). CONCLUSION: The active ingredients in E. ulmoides leaves regulating nonalcoholic fatty liver disease are mainly flavonoids and phenolics. EUL 50 may play a role in lowering lipids by regulating PPARγ expression through inducing autophagy.

Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: a clinicopathological study of 66 cases comparing cases with prior history of treatment to those without.

AIMS: Myeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated. METHODS: Retrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease. RESULTS: Of these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, -5/5q- and/or -7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05). CONCLUSIONS: Myeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.

Quantitative detection of Aflatoxin B1 by subpixel CNN regression.

Aflatoxin is a highly toxic substance dispersed in peanuts, which seriously harms the health of humans and animals. In this paper, we propose a new method for aflatoxin B1(AFB1) detection inspired by quantitative remote sensing. Firstly, we obtained the relative content of AFB1 at the sub-pixel level by subpixel decomposition (endmember extraction, nonnegative matrix decomposition). Then we modified the transfer learning models (LeNet5, AlexNet, VGG16, and ResNet18) to construct a deep learning regression network for quantitative detection of AFB1. There are 67,178 pixels used for training and 67,164 pixels used for testing. After subpixel decomposition, each aflatoxin pixel was determined to contain content, and each pixel had 400 hyperspectral values (415-799 nm). The experimental results showed that, among the four models, the modified ResNet18 model achieved the best effect, with R2 of 0.8898, RMSE of 0.0138, and RPD of 2.8851. Here, we implemented a sub-pixel model for quantitative AFB1 detection and proposed a regression method based on deep learning. Meanwhile, the modified convolution classification model has high predictive ability and robustness. This method provides a new scheme in designing the sorting machine and has practical value.

[Discovery and activity verification of reniformin A as an anti-tumor leading compound].

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

Human esophageal fibroblast-derived exosomal miR-21 reduced the cisplatin sensitivity to esophageal carcinoma EC9706 cells.

The objective of this study was to investigate the effect of human esophageal fibroblast-derived exosomal miR-21 on cisplatin sensitivity against esophageal squamous EC9706 cells. EC9706 cells were co-cultured indirectly with human esophageal fibroblasts (HEF) or miR-21 mimics transfected-HEF in the transwell system. The exosomes in HEF-culture conditioned medium were extracted by differential ultracentrifugation. EC9706 cells were co-cultured with HEF-derived exosomes directly. The cisplatin sensitivity against EC9706 cells was revealed via half maximal inhibitory concentration (IC50) values using MTT assay. The expressions of miR-21, programmed cell death 4 (PDCD4) mRNA, and gene of phosphate and tension homology deleted on chromosome ten (PTEN) mRNA were determined by qRT-PCR. The changes of the protein level were detected using western blot assay. IC50 values of cisplatin against EC9706 cells were increased after EC9706 cells were co-cultured with either HEF or exosomes derived from miR-21 mimics-transfected HEF. Following the increased level of miR-21, the mRNA expression and protein levels of PTEN and PDCD4 were decreased in EC9706 cells. The cisplatin sensitivity to EC9706 cells was reduced by HEF-derived exosomal miR-21 through targeting PTEN and PDCD4. This study suggested that non-tumor cells in the tumor micro-environment increased the tumor anti-chemotherapy effects through their exosomes.

Infantile leukemia-What factors determine its distinct biological nature? Clinicopathological study of 78 cases.

INTRODUCTION: Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. METHODS: We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. RESULTS: Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. CONCLUSION: The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.

Characterization of an endoplasmic reticulum stress-related signature to evaluate immune features and predict prognosis in glioma.

Endoplasmic reticulum (ER) stress has considerable impact on cell growth, proliferation, metastasis, invasion, angiogenesis and chemoradiotherapy resistance in various cancers. However, the effect of ER stress on the outcomes of glioma patients remains unclear. In this study, we established an ER stress risk model based on The Cancer Genome Atlas (TCGA) glioma data set to reflect immune characteristics and predict the prognosis of glioma patients. Survival analysis indicated that there were significant differences in the overall survival (OS) of glioma patients with different ER stress-related risk scores. Moreover, the ER stress-related risk signature, which was markedly associated with the clinicopathological properties of glioma patients, could serve as an independent prognostic indicator. Functional enrichment analysis revealed that the risk model correlated with immune and inflammation responses, as well as biosynthesis and degradation. In addition, the ER stress-related risk model indicated an immunosuppressive microenvironment. In conclusion, we present an ER stress risk model that is an independent prognostic factor and indicates the general immune characteristics in the glioma microenvironment.

Pulmonary artery intimal sarcoma mimicking pulmonary thromboembolism: A case report.

RATIONALE: Pulmonary artery intimal sarcoma is a rare tumor with exceptionally high mortality and easily misdiagnosed as pulmonary thromboembolism pulmonary thromboembolism (PTE) due to the nonspecific clinical presentation and symptom. Misdiagnosis or untimely diagnosis makes the disease progress to an advanced stage and eventually leads to a poor prognosis. PATIENT CONCERNS: A 37-year-old Chinese female presented with chest tightness and dyspnea for 3 months. Echocardiography and chest computed tomography revealed an intraluminal obstruction of the pulmonary arteries. Tests of serum tumor makers showed slight elevation for carbohydrate antigen-125, and α-fetoprotein. PTE was suspected according to the radiological and laboratory findings. DIAGNOSIS: Microscopic findings of the presumed thrombus showed prominent myxoid and edematous background with atypical spindled cells and curvilinear vascularity. Immunohistochemical staining demonstrated that the atypical spindled cells were positive for vimentin but negative for CK, S100, SMA, desmin, CD68, STAT6, CD34, ß-catenin, ALK-p80, p53, and MDM2. According to the radiological and pathological findings, the diagnosis of fibrosarcoma of pulmonary artery was made. INTERVENTIONS: The patient underwent surgical resection and the mass was excised as completely as possible. OUTCOME: Follow-up information showed no evidence of recurrence or metastasis after 3 months postresection. LESSONS: Because of the low incidence rate, nonspecific clinical symptoms, and radiological findings, primary fibrosarcoma of the pulmonary artery is commonly misdiagnosed as PTE. Pathological examination is necessary to confirm the diagnosis.

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems have revolutionized traditional gene-editing tools and are a significant tool for ameliorating gene defects. Characterized by high target specificity, extraordinary efficiency, and cost-effectiveness, CRISPR/Cas systems have displayed tremendous potential for genetic manipulation in almost any organism and cell type. Despite their numerous advantages, however, CRISPR/Cas systems have some inherent limitations, such as off-target effects, unsatisfactory efficiency of delivery, and unwanted adverse effects, thereby resulting in a desire to explore approaches to address these issues. Strategies for improving the efficiency of CRISPR/Cas-induced mutations, such as reducing off-target effects, improving the design and modification of sgRNA, optimizing the editing time and the temperature, choice of delivery system, and enrichment of sgRNA, are comprehensively described in this review. Additionally, several newly emerging approaches, including the use of Cas variants, anti-CRISPR proteins, and mutant enrichment, are discussed in detail. Furthermore, the authors provide a deep analysis of the current challenges in the utilization of CRISPR/Cas systems and the future applications of CRISPR/Cas systems in various scenarios. This review not only serves as a reference for improving the maturity of CRISPR/Cas systems but also supplies practical guidance for expanding the applicability of this technology.