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BackgroundUC patients suffer more from colorectal cancer (CRC) than the general population, which increases with disease duration. Early colonoscopy is difficult because ulcerative colitis-associated colorectal cancer (UCAC) lesions are flat and multifocal. Our study aimed to identify promising UCAC biomarkers that are complementary endoscopy strategies in the early stages.MethodsThe datasets may be accessed from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The co-expressed modules of UC and CRC were determined via weighted co-expression network analysis (WGCNA). The biological mechanisms of the shared genes were exported for analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To identify protein interactions and hub genes, a protein-protein interaction network and CytoHubba analysis were conducted. To evaluate gene expression, external datasets and experimental validation of human colon tissues were utilized. The diagnostic value of core genes was examined through receiver operating characteristic (ROC) curves. Immune infiltration analysis was employed to investigate the associations between immune cell populations and hub genes.ResultsThree crucial modules were identified from the WGCNA of UC and CRC tissues, and 33 coexpressed genes that were predominantly enriched in the NF-κB pathway were identified. Two biomarkers (CXCL1 and BCL6) were identified via Cytoscape and validated in external datasets and human colon tissues. CRC patients expressed CXCL1 at the highest level, whereas UC and CRC patients showed higher levels than the controls. The UC cohort expressed BCL6 at the highest level, whereas the UC and CRC cohorts expressed it more highly than the controls. The hub genes exhibited significant diagnostic potential (ROC curve > 0.7). The immune infiltration results revealed a correlation among the hub genes and macrophages, neutrophils and B cells.ConclusionsThe findings of our research suggest that BCL6 and CXCL1 could serve as effective biomarkers for UCAC surveillance. Additionally, they demonstrated a robust correlation with immune cell populations within the CRC tumour microenvironment (TME). Our findings provide a valuable insight about diagnosis and therapy of UCAC.

Abstract Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/ . Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1–10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3–39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

Background: Various studies highlighted that immune cell-mediated inflammatory processes play crucial roles in the progression and treatment of hepatocellular carcinoma (HCC). However, the immune microenvironment of HCC is still poorly characterized. Exploring the role of immune-related genes (IRGs) and describing the immune landscape in HCC would provide insights into tumor-immune co-evolution along HCC progression. Methods: We integrated the datasets with complete prognostic information from the Cancer Genome Atlas (TCGA) database and GEO DataSets (GSE14520, GSE76427, and GSE54236) to construct a novel immune landscape based on the Cibersort algorithm and reveal the prognostic signature in HCC patients. Results: To describe the tumor microenvironment (TME) in HCC, immune infiltration patterns were defined using the CIBERSORT method, and a prognostic signature contains 5 types of immune cells, including 3 high-risk immune cells (T.cells. CD4. memory. resting, Macrophages.M0, Macrophages.M2) and 2 low-risk immune cells (Plasma. cells, T.cells.CD8), were finally constructed. A novel prognostic index, based on prognostic immune risk score (pIRG), was developed using the univariate Cox regression analyses and LASSO Cox regression algorithm. Furthermore, the ROC curve and KM curve showed that the TME signatures had a stable value in predicting the prognosis of HCC patients in the internal training cohort, internal validation, and external validation cohort. Differential genes analysis and qPCR experiment showed that the expression levels of AKR1B10, LAPTM4B, MMP9, and SPP1 were significantly increased in high-risk patients, while the expression of CD5L was lower. Further analysis found that AKR1B10 and MMP9 were associated with higher M0 macrophage infiltration, while CD5L was associated with higher plasma cell infiltration. Conclusions: Taken together, we performed a comprehensive evaluation of the immune landscape of HCC and constructed a novel and robust prognostic prediction model. AKR1B10, LAPTM4B, MMP9, SPP1, and CD5L were involved in important processes in the HCC tumor microenvironment and were expected to become HCC prediction markers and potential targets of treatment.

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the β-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and β-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/β-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/β-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

Abstract Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.

Abstract Background During the eleven years from 2010 to 2021, preliminary statistics have shown that Fuwai Hospital completed 23,571 mechanical valve replacements for various types of valves, and 1139 mechanical valve replacements were performed in Guangyuan First People's Hospital. Only two patients developed valve leaflet escape, so valve leaflet escape is a rare postoperative complication. Case presentation In 2010 and 2021, two patients were selected after they had unilateral leaflet escape after having mechanical valve replacements in Fuwai Hospital of Chinese Academy of Medical Sciences and Guangyuan First People's Hospital. Both patients underwent reoperations with the classic operation and the new bileaflet mechanical prosthetic heart valve was sutured. The treatment of detached single lobe and distal vessel was comprehensively determined, and the condition was treated according to the patient's symptoms, CT results, ultrasound results and other test results, as well as whether this detached lobe caused any abnormal hemodynamics of the distal vessel. The patient with mechanical aortic valve escape completed the 10-year follow-up, and patient with mechanical mitral valve escape completed the 3-month follow-up. there was no thrombosis or hematoma at the embolic site; the patient had no lower limb symptoms. Conclusions The reason for the leaflet escape may be related to the valve design and the leaflet material. If the detached leaflets are damaged and if the distal blood vessels are affected, simultaneous surgical treatment is required. Those patients whose vessels were not damaged by the valve lobe should be carefully monitored.

Abstract Background Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. Methods CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. Results We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. Conclusions This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.

BackgroundThoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients.MethodsPublically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets.ResultsWGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association.ConclusionsTAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.

Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Herein, an efficient and accurate high-performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of 5 bioactive compounds in rat plasma following oral administration of Zuogui Pill. Because drug absorption and distribution differ under physiological and pathological conditions, the established method was used to quantify blood components and dynamic change in osteoporotic rats with different syndrome types. Moreover, integrated pharmacokinetic study was conducted to describe the overall pharmacokinetic characteristics of traditional Chinese medicine. The results showed that the absorption, distribution, and metabolism of Zuogui Pill varied widely under different states. The bioavailability of most active components showed significant advantages in osteoporotic rats with kidney-yin-deficiency, which corresponds to the opinion that Zuogui Pill has the effect of nourishing kidney-yin. It is hoped that this finding could interpret the pharmacodynamic substances and mechanism of Zuogui Pill in the treatment of osteoporosis with kidney-yin-deficiency.

A photon-counting distributed free-space spectroscopy is proposed and demonstrated using lidar technique. It is suitable for remote spectrum analysis with range resolution over wide band.

BackgroundGlioblastoma (GBM) is a fatal brain tumor with no effective treatment. The specific GBM tumor immune microenvironment (TIME) may contribute to resistance to immunotherapy, a tumor therapy with great potential. Thus, an in-depth understanding of the characteristics of tumor-infiltrating immune cells is essential for exploring biomarkers in GBM pathogenesis and immunotherapy.MethodsWe estimated the relative abundances of 25 immune cell types in 796 GBM samples using single sample gene set enrichment analysis (ssGSEA). Unsupervised clustering was used to identify different GBM-associated TIME immune cell infiltration (GTMEI) patterns. The GTMEIscore system was constructed with principal component analysis (PCA) to determine the immune infiltration pattern of individual tumors.ResultsWe revealed three distinct GTMEI patterns with different clinical outcomes and modulated biological pathways. We developed a scoring system (GTMEIscore) to determine the immune infiltration pattern of individual tumors. We comprehensively analyzed the genomic characteristics, molecular subtypes and clinicopathological features as well as proteomic, phosphoproteomic, acetylomic, lipidomic and metabolomic properties associated with the GTMEIscore and revealed many novel dysregulated pathways and precise targets in GBM. Moreover, the GTMEIscore accurately quantified the immune status of many other cancer types. Clinically, the GTMEIscore was found to have significant potential therapeutic value for chemotherapy/radiotherapy, immune checkpoint inhibitor (ICI) therapy and targeted therapy.ConclusionsFor the first time, we employed a multilevel and multiplatform strategy to construct a multidimensional molecular map of tumors with different immune infiltration patterns. These results may provide theoretical basises for identifying more effective predictive biomarkers and developing more effective drug combination strategies or novel immunotherapeutic agents for GBM.

Doppler wind lidar (DWL) uses the optical Doppler effect to measure atmospheric wind speed with high spatial-temporal resolution and long detection range and has been widely applied in scientific research and engineering applications. With the development of related technology, especially laser and detector technology, the performance of the DWL has significantly improved for the past few decades. DWL utilizes different principles and different tracers to sense the wind speed from the ground to the mesosphere, which leads to the difference in choosing the laser working wavelength. This article will review the working wavelength consideration of DWL, and typical DWLs will present from ultraviolet to near-infrared, after which three typical applications will be shown.

AimsVarious kinds of surgical strategies and prostheses have been advocated to improve short-term and long-term outcomes in type A aortic dissection (TAAD). Large-scale repair of the pathological aorta is hard to generalize due to complex procedures. We aimed to investigate the performance, effectiveness and safety of a novel Sutureless Integrated Stented (SIS) graft prosthesis in TAAD patients undergoing total arch replacement (TAR) and frozen elephant trunk (FET) implantation surgery.MethodsAll patients admitted to Fuwai Hospital were prospectively screened. Urgent or scheduled surgery was arranged for eligible patients. The primary endpoint was operative mortality. Key secondary endpoints included stroke, spinal cord injury, unexpected aortic reoperation, and 1-year survival. Discharged patients were followed up with computed tomography angiography and transthoracic echocardiography at 3 months, 6 months, and 1 year after surgery. Performance, effectiveness and safety analyses were performed in those patients.ResultsBetween August 1 and September 3, 2020, ten TAAD patients were enrolled in this study and successfully implanted with the SIS graft prosthesis. The median (IQR) age was 56.50 (43.75, 66.75) years (range from 31 to 75), and seven patients were male (70.0%). All patients underwent ascending aorta replacement + TAR + FET and additional procedures when necessary. The median (IQR) operation time, cardiopulmonary bypass time and cross clamp time were 270.50 (218.50, 312.50), 110.00 (88.00, 125.75), 69.50 (51.25, 82.75) min, respectively. Of note, the median (IQR) circulatory arrest time was 9.00 (8.00, 9.00) min (range from 4 to 12). The median (IQR) lowest nasopharyngeal temperature was 26.75 (25.98, 27.67) °C. Follow-up was 100% completed. During the 1-year follow-up, no patients died, no severe adverse events occurred, and rate of freedom from aortic reintervention was 100%.ConclusionsThe SIS graft prosthesis was implanted in a novel sutureless way, which simplified the surgical procedure, shortened the circulatory arrest time and avoided deep hypothermia. The preliminary clinical outcomes and follow-up outcomes demonstrated the effectiveness and safety of this prosthesis. A large-scale trial is being conducted to further assess these findings.

Objective: The duration of hypothermic circulatory arrest (HCA) is one of the important factors affecting the prognosis of arch surgery, which is still controversial. The purpose of this study was to investigate the effect of HCA duration on early prognosis in type A aortic dissection (TAAD) patients who underwent arch surgery in our center.Methods: All consecutive patients who underwent surgical treatment for TAAD in Fuwai Hospital from January 2013 to December 2018 were included in this study and divided into four quartile groups based on HCA time. Baseline characteristics, perioperative indicators, and early mortality were statistically analyzed by propensity score matching (PSM) and restricted cubic spline (RCS) method. Perioperative adverse events were confirmed according to the American STS database and Penn classification.Results: About 1,018 consecutive patients (mean age 49.11 ± 1.4 years, male 74.7%) with TAAD treated surgically were eventually included in this study. After PSM, with the prolongation of HCA time, the surgical mortality rates of group [2,15], (15,18], (18,22], and (22,73] were 4.1, 6.6, 7.8, and 10.9% with p = 0.041, respectively. As shown in RCS, the mortality rate increased sharply after the HCA time exceeded 22 min. And from the subgroup analysis, the HCA time of 22 min or less was associated with better clinical outcomes (OR 2.09, 95%CI 1.25–3.45, p = 0.004).Conclusions: The early mortality increases significantly with the duration of HCA time when arch surgery was performed. And multiple systems throughout the body can be adversely affected.

Background: This study employed three surgical techniques: total arch replacement (TAR) with frozen elephant trunk (FET), aortic balloon occlusion technique (ABO) and hybrid aortic arch repair (HAR) on patients with type I aortic dissection in Fuwai Hospital, aiming to compare the early outcomes of these surgical armamentariums.Methods: From January 2016 to December 2018, an overall 633 patients (431 of TAR+FET, 122 of HAR, and 80 of ABO) with type I aortic dissection were included in the study. Thirty-day mortality, stroke, paraplegia, re-exploration for bleeding, and renal replacement therapy were compared using the matching weight method (MWM).Results: After MWM process, the baseline characteristics were comparable among three TAR groups. It showed that ABO group had the longest cardiopulmonary bypass (p < 0.001) and aortic cross-clamp time (p < 0.001), while the operation time was longest in the HAR group (p = 0.039). There was no significant difference in 30-day mortality among groups (p = 0.783). Furthermore, the incidence of stroke (p = 0.679), paraplegia (p = 0.104), re-exploration for bleeding (p = 0.313), and CRRT (p = 0.834) demonstrated no significant difference. Of note, no significant differences were found regarding these outcomes even before using MWM.Conclusions: Based on the early outcomes, the three TAR approaches were equally applicable to type I aortic dissection. We may choose the specific procedure relatively flexibly according to patient status and surgeon's expertise. Importantly, long-term investigations are warranted to determine whether above approaches remain to be of equivalent efficacy and safety.