Cellular senescence gene TACC3 associated with colorectal cancer risk via genetic and DNA methylated alteration.

Cell senescence genes play a vital role in the pathogenesis of colorectal cancer, a process that may involve the triggering of genetic variations and reversible phenotypes caused by epigenetic modifications. However, the specific regulatory mechanisms remain unclear. Using CellAge and The Cancer Genome Atlas databases and in-house RNA-seq data, DNA methylation-modified cellular senescence genes (DMCSGs) were validated by Support Vector Machine and correlation analyses. In 1150 cases and 1342 controls, we identified colorectal cancer risk variants in DMCSGs. The regulatory effects of gene, variant, and DNA methylation were explored through dual-luciferase and 5-azacytidine treatment experiments, complemented by multiple database analyses. Biological functions of key gene were evaluated via cell proliferation assays, SA-ß-gal staining, senescence marker detection, and immune infiltration analyses. The genetic variant rs4558926 in the downstream of TACC3 was significantly associated with colorectal cancer risk (OR = 1.35, P = 3.22 × 10-4). TACC3 mRNA expression increased due to rs4558926 C > G and decreased DNA methylation levels. The CpG sites in the TACC3 promoter region were regulated by rs4558926. TACC3 knockdown decreased proliferation and senescence in colorectal cancer cells. In addition, subjects with high-TACC3 expression presented an immunosuppressive microenvironment. These findings provide insights into the involvement of genetic variants of cellular senescence genes in the development and progression of colorectal cancer.

Factors affecting the intraoperative calculi excretion during flexible ureteroscopy lithotripsy: an in vitro analysis.

OBJECTIVE: To explore the parameters influencing intraoperative calculi excretion (ICE) during flexible ureteroscopy lithotripsy (fURL) using in vitro simulation experiments. METHODS: 3D-printed human kidney models were used to simulate the elimination of gravel during fURL. The factors influencing the ICE during fURL were analyzed by comparing the effects of different degrees of hydronephrosis (mild, moderate, and severe), surgical positions (supine and lateral position), ratios of endoscope-sheath diameter (RESD) (0.625, 0.725, and 0.825), gravel sizes (0.50-1.00 mm, 0.25-0.50 mm, and 0.10-0.25 mm), and ureteral access sheaths (UASs) (traditional UAS and negative-pressure UAS) on ICE. RESULTS: The impacts of various UAS, RESD, degree of hydronephrosis, surgical positions, and gravel sizes on ICE were all significant (p < 0.05). We found no evidence of multicollinearity for all the independent variables, and the linear regression equation fitted as ICE ( g / min ) = 0.102 + 0.083 ∗ UAS grade - 0.050 ∗ RESD grade - 0.048 ∗ hydronephrosis grade + 0.065 ∗ position grade - 0.027 ∗ gravel size grade (R2 = 0.569). CONCLUSION: Employing negative-pressure UAS, smaller RESD, milder hydronephrosis, lateral position, and smaller gravel size contribute to improved ICE during fURL. Among them, the adoption of negative-pressure UAS had the most substantial effects.

Unveiling immunogenic cell death-related genes in colorectal cancer: an integrated study incorporating transcriptome and Mendelian randomization analyses.

Immunogenic cell death (ICD), a type of cell death that activates the tumor-specific immune response and thus exerts anti-tumor effects, is an emerging target in tumor therapy, but research on ICD-related genes (ICDGs) in colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through RNA sequencing for tissue samples from CRC patients and integration with The Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.

The effect of reinforcing sutures and trans-anal drainage tube on the outcome of laparoscopic resection for rectal cancer: propensity score­matched analysis.

OBJECTIVES: Laparoscopic resection for rectal cancer is currently the predominant treatment modality for rectal tumors, with an ongoing focus on reducing the incidence of postoperative complications. In an effort to decrease the occurrence of anastomotic leakage, two additional steps worth considering are reinforcing the anastomosis with a barbed suture and retaining an anal drain as part of the procedure. The results of the operation were analyzed by comparing them to cases where the anastomosis was performed with a stapler alone. METHODS: This study retrospectively analyzed patients who underwent laparoscopic radical rectal cancer surgery between July 2020 and March 2023. The patients were categorized into three cohorts based on the postoperative management following instrumented anastomosis: cohort A, the instrumented anastomosis alone group; cohort B, the reinforced suture group; and cohort C, the reinforced suture and indwelling transanal drainage tube group. Propensity score matching was performed twice in a 1:1 ratio, comparing cohort B to cohort A and cohort C to cohort B. The objective was to compare the benefits and drawbacks among the different groups in terms of operative time, postoperative outcomes and operative costs. RESULTS: 529 patients with laparoscopic resection for rectal cancer were eligible for inclusion. the instrumented anastomosis alone group, reinforced suture group and the reinforced suture and indwelling transanal drainage tube group were performed in 205 patients, 198 patients and 126 patients, respectively. Cohort A and Cohort B differed in three variables after PSM: total operative time (p = 0.018), postoperative hospital stay (p < 0.001) and incidence of anastomotic leakage (p = 0.038). Cohort B had a longer total operative time, shorter postoperative hospital stay and a lower incidence of anastomotic leakage. Similarly, cohort C had less postoperative drainage (P = 0.01) and a longer postoperative hospital stay (P = 0.003) when cohort B and cohort C were matched for propensity scores. There was no significant difference in the cost of surgery between the three cohorts. CONCLUSIONS: The incorporation of barbed suture reinforcement significantly reduces the occurrence of postoperative anastomotic leakage in rectal cancer surgeries. On the other hand, although trans-anal drainage was used as an additional measure to the reinforcement suture of the anastomosis, the utilization of trans-anal drainage tubes does not demonstrate a significant improvement in surgical outcomes.

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma.

Background: Lysosomes are essential for the development and recurrence of cancer. The relationship between a single lysosome-related gene and cancer has previously been studied, but the relationship between the lysosome-related genes (LRGs) and colon adenocarcinoma (COAD) remains unknown. This research examined the role of lysosome-related genes in colon adenocarcinoma. Methods: 28 lysosome-related genes associated with prognosis (PLRGs) were found by fusing the gene set that is differently expressed between tumor and non-tumor in colon adenocarcinoma with the gene set that is related to lysosomes. Using consensus unsupervised clustering of PLRGs, the colon adenocarcinoma cohort was divided into two subtypes. Prognostic and tumor microenvironment (TME) comparisons between the two subtypes were then made. The PLRGs_score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify each patient's prognosis and provide advice for treatment. Lastly, Western Blot and immunohistochemistry (IHC) were used to identify MOGS expression at the protein level in colon adenocarcinoma tissues. Results: PLRGs had more somatic mutations and changes in genetic level, and the outcomes of the two subtypes differed significantly in terms of prognosis, tumor microenvironment, and enrichment pathways. Then, PLRGs_score was established based on two clusters of differential genes in the cancer genome atlas (TCGA) database, and external verification was performed using the gene expression omnibus (GEO) database. Then, we developed a highly accurate nomogram to enhance the clinical applicability of the PLRGs_score. Finally, a higher PLRGs_score was associated with a poorer overall survival (OS), a lower tumor mutation burden (TMB), a lower cancer stem cell (CSC) index, more microsatellite stability (MSS), and a higher clinical stage. MOGS was substantially elevated at the protein level in colon adenocarcinoma as additional confirmation. Conclusion: Overall, based on PLRGs, we identified two subtypes that varied significantly in terms of prognosis and tumor microenvironment. Then, in order to forecast patient prognosis and make treatment suggestions, we developed a diagnostic model with major significance for prognosis, clinical relevance, and immunotherapy. Moreover, we were the first to demonstrate that MOGS is highly expressed in colon adenocarcinoma.

Machine learning-based glycolysis-associated molecular classification reveals differences in prognosis, TME, and immunotherapy for colorectal cancer patients.

Background: Aerobic glycolysis is a process that metabolizes glucose under aerobic conditions, finally producing pyruvate, lactic acid, and ATP for tumor cells. Nevertheless, the overall significance of glycolysis-related genes in colorectal cancer and how they affect the immune microenvironment have not been investigated. Methods: By combining the transcriptome and single-cell analysis, we summarize the various expression patterns of glycolysis-related genes in colorectal cancer. Three glycolysis-associated clusters (GAC) were identified with distinct clinical, genomic, and tumor microenvironment (TME). By mapping GAC to single-cell RNA sequencing analysis (scRNA-seq), we next discovered that the immune infiltration profile of GACs was similar to that of bulk RNA sequencing analysis (bulk RNA-seq). In order to determine the kind of GAC for each sample, we developed the GAC predictor using markers of single cells and GACs that were most pertinent to clinical prognostic indications. Additionally, potential drugs for each GAC were discovered using different algorithms. Results: GAC1 was comparable to the immune-desert type, with a low mutation probability and a relatively general prognosis; GAC2 was more likely to be immune-inflamed/excluded, with more immunosuppressive cells and stromal components, which also carried the risk of the poorest prognosis; Similar to the immune-activated type, GAC3 had a high mutation rate, more active immune cells, and excellent therapeutic potential. Conclusion: In conclusion, we combined transcriptome and single-cell data to identify new molecular subtypes using glycolysis-related genes in colorectal cancer based on machine-learning methods, which provided therapeutic direction for colorectal patients.

The Involvement of Ubiquitination and SUMOylation in Retroviruses Infection and Latency.

Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be temporarily transcriptional silencing in infected cells, which makes retroviral infection incurable. Although many cellular restriction factors interfere with various steps of the life cycle of retroviruses and the formation of viral latency, viruses can utilize viral proteins or hijack cellular factors to evade intracellular immunity. Many post-translational modifications play key roles in the cross-talking between the cellular and viral proteins, which has greatly determined the fate of retroviral infection. Here, we reviewed recent advances in the regulation of ubiquitination and SUMOylation in the infection and latency of retroviruses, focusing on both host defense- and virus counterattack-related ubiquitination and SUMOylation system. We also summarized the development of ubiquitination- and SUMOylation-targeted anti-retroviral drugs and discussed their therapeutic potential. Manipulating ubiquitination or SUMOylation pathways by targeted drugs could be a promising strategy to achieve a "sterilizing cure" or "functional cure" of retroviral infection.

Systems Network Pharmacology-Based Prediction and Analysis of Potential Targets and Pharmacological Mechanism of Actinidia chinensis Planch. Root Extract for Application in Hepatocellular Carcinoma.

Purpose: Traditional Chinese medicine (TCM) sometimes plays a crucial role in advanced cancer treatment. Despite the significant therapeutic efficacy in hepatocellular carcinoma (HCC) that Actinidia chinensis Planch root extract (acRoots) has proven, its complex composition and underlying mechanism have not been fully elucidated. Therefore, this study analyzed the multiple chemical compounds in acRoots and their targets via network pharmacology and bioinformatics analysis, with the overarching goal of revealing the potential mechanisms of the anti-HCC effect. Methods: The main ingredients contained in acRoots were initially screened from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the candidate bioactive ingredient targets were identified using DrugBank and the UniProt public databases. Second, the biological processes of the targets of active molecules filtered from the ingredients of acRoots were evaluated using gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Third, weighted gene coexpression network analysis (WGCNA) was performed to identify gene coexpression modules associated with HCC. The hub genes of acRoots in HCC were defined via contrasting the above module eigengenes with candidate target genes of acRoots. Furthermore, the target-pathway network was analyzed to explore the mechanism for anti-HCC effect of hub genes. Kaplan-Meier plotter database analysis was performed to validate the hub genes of acRoots correlation with prognostic values in HCC. In order to verify the results of the network pharmacological analysis, we performed a molecular docking approach on the active ingredients and key targets using the Discovery Studio software. The viability of SMMC-7721 and HL-7702 cells was determined by Cell counting kit-8 (CCK-8) after being treated with different concentrations of (+)-catechin (0, 50, 100, 150, 200, and 250 g/ml) for 24, 48, and 72 hours, respectively. Finally, qRT-PCR and Western blot involving human hepatocarcinoma cells were utilized to verify the impact of (+)-catechin on the hub genes associated with prognosis. Results: 6 out of 26 active ingredients extracted from TCMSP were deemed as the core ingredients of acRoots. 175 bioactive-ingredient targets of acRoots were obtained and a bioactive-ingredient targets network was established correspondingly. The biological processes (BP) of target genes mainly involved processes, such as toxic substance and wounding. The results of KEGG pathways indicated that the target genes were mainly enriched in pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, and other pathways. Also, the two hub genes (i.e., ESR1 and CAT) were closely associated with the prognosis of HCC patients. As a consequence, we predicated a series of signaling pathways, including estrogen signaling pathway and longevity regulation pathway, through which acRoots could facilitate the treatment for HCC. The molecular docking experiment ascertained that ESR1 and CAT had an effective binding force with (+)-catechin, one of the core ingredients of acRoots. Furthermore, (+)-catechin inhibited SMMC-7721 cell growth in a dose-dependent manner and a time-dependent manner. Finally, we suggest that the expression level of ESR1 and CAT is positively related to the (+)-catechin concentrations in in-vitro experiments. Conclusion: The bioactive ingredients of acRoots, including quercetin, (+)-catechin, beta-sitosterol, and aloe-emodin, have synergistic interactions in reinforcing the anticancer effect in HCC. Evidently, acRoots took effect by regulating multitargets and multipathways through its active ingredients. Further, (+)-catechin, the possible paramount anti-HCC active ingredient in acRoots, helped improve the prognosis of HCC patients by increasing the expression of ESR1 and CAT. Additionally, the findings yielded provide a conceptual guidance for the clinical treatment of HCC and the methods adopted are potentially applicable in the future comprehensive analysis of the underlying mechanisms of TCMs.

Identification of predictive factors for post-transarterial chemoembolization liver failure in hepatocellular carcinoma patients: A retrospective study.

BACKGROUND: Post-transarterial chemoembolization (TACE) liver failure occurs frequently in hepatocellular carcinoma (HCC) patients. The identification of predictors for post-TACE liver failure is of great importance for clinical decision-making in this population. AIM: To investigate the occurrence rate and predictive factors of post-TACE liver failure in this retrospective study to provide clues for decision-making regarding TACE procedures in HCC patients. METHODS: The clinical records of HCC patients treated with TACE therapy were reviewed. Baseline clinical characteristics and laboratory parameters of these patients were extracted. Logistic models were used to identify candidates to predict post-TACE liver failure. RESULTS: A total of 199 HCC patients were enrolled in this study, and 70 patients (35.2%) developed post-TACE liver failure. Univariate and multivariate logistic models indicated that microspheres plus gelatin embolization and main tumor size > 5 cm were risk predictors for post-TACE liver failure [odds ratio (OR): 4.4, 95% confidence interval (CI): 1.2-16.3, P = 0.027; OR: 2.3, 95%CI: 1.05-5.3, P = 0.039, respectively]. Conversely, HCC patients who underwent tumor resection surgery before the TACE procedure had a lower risk for post-TACE liver failure (OR: 0.4, 95%CI: 0.2-0.95, P = 0.039). CONCLUSION: Microspheres plus gelatin embolization and main tumor size might be risk factors for post-TACE liver failure in HCC patients, while prior tumor resection could be a favorable factor reducing the risk of post-TACE liver failure.

Automatic quantification and grading of hip bone marrow oedema in ankylosing spondylitis based on deep learning.

OBJECTIVE: This study has developed a new automatic algorithm for the quantificationy and grading of ankylosing spondylitis (AS)-hip arthritis with magnetic resonance imaging (MRI). METHODS: (1) This study designs a new segmentation network based on deep learning, and a classification network based on deep learning. (2) We train the segmentation model and classification model with the training data and validate the performance of the model. (3) The segmentation results of inflammation in MRI images were obtained and the hip joint was quantified using the segmentation results. RESULTS: A retrospective analysis was performed on 141 cases; 101 patients were included in the derived cohort and 40 in the validation cohort. In the derivation group, median percentage of bone marrow oedema (BME) for each grade was as follows: 36% for grade 1 (<15%), 42% for grade 2 (15-30%),and 22% for grade 3 (≥30%). The accuracy of 44 cases on 835 AS images was 85.7%. Our model made 31 correct decisions out of 40 AS test cases. This study showed that THE accuracy rate 85.7%. CONCLUSIONS: An automatic computer-based analysis of MRI has the potential of being a useful method for the diagnosis and grading of AS hip BME.

Anlotinib Suppresses Oral Squamous Cell Carcinoma Growth and Metastasis by Targeting the RAS Protein to Inhibit the PI3K/Akt Signalling Pathway.

Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities. Unfortunately, multidrug resistant is one of the important obstacles that causes cancer chemotherapy failure. Anlotinib, which has recently been proven to have good antitumour effects, is a novel multitargeted tyrosine kinase inhibitor. However, there are few studies of the anlotinib-associated mechanism in OSCC and its underlying molecular mechanism. In our study, in vitro models of human oral squamous cell carcinoma HSC-3 cells were used to determine the efficacy of anlotinib. On the one hand, we showed that anlotinib treatment significantly reduced the viability and proliferation of HSC-3 cells and decreased cell migration by inhibiting the activation of the Akt phosphorylation pathway. On the other side, anlotinib inhibited PI3K/Akt/Bad phosphorylation and promoted apoptosis of HSC-3 cells by activating RAS protein expression. In brief, these results indicated that anlotinib had prominent antitumour activity in OSCC, mainly by inhibiting the PI3K/Akt phosphorylation pathway. This work provides evidences and a basic principle for using anlotinib to treat patients with OSCC for clinical research.

Firmicutes and Blautia in gut microbiota lessened in chronic liver diseases and hepatocellular carcinoma patients: a pilot study.

The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.

Association between cystatin C and diabetic retinopathy among type 2 diabetic patients in China: a Meta-analysis.

AIM: To explore the correlation between cystatin C (Cys-C) and diabetic retinopathy (DR) in those patients with type 2 diabetes mellitus (DM) in China. METHODS: Articles were collected from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Google Scholar. Quality and risk of bias within included studies was assessed using the Newcastle-Ottawa scale (NOS). Heterogeneity was determined by using Cochran's Q-test and Higgins I 2 statistics. Mean differences (MDs) and 95% confidence intervals (CIs) of Cys-C within the diabetes without retinopathy (DWR) and DR, DWR and non-proliferative diabetic retinopathy (NPDR), NPDR and proliferative diabetic retinopathy (PDR) were collected by using random-effects model because of high heterogeneity. Meta-analysis was conducted based on 23 articles of 2331 DR including NPDR and PDR patients and 2023 DWR patients through Review Manager 5.3. Subgroup analyses were also performed according to DM duration, body mass index (BMI), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C), sample origins and methods. Publication bias was assessed by the funnel plot. RESULTS: Cys-C level in DR patients was increased compared with that of DWR (total MD: 0.69, 95%CI: 0.41 to 0.97, Z=4.79, P<0.01). Besides, the synthesized results of the studies showed the similar findings in the DWR vs NPDR group (total MD: 0.29, 95%CI 0.20 to 0.39, Z=6.02, P<0.01) and the NPDR vs PDR group (total MD: 0.63, 95%CI 0.43 to 0.82, Z=6.33, P<0.01). Heterogeneity of most of the subgroup analyses was still obvious (I 2≥50%, P<0.1). Forest plots of different subgroups indicated that there was a slight increase of Cys-C during the period between DWR and DR, DWR and NPDR, NPDR and PDR. Funnel plot showed that there was no significant publication bias. CONCLUSION: The elevated Cys-C is closely related with DR and probably plays a critical role in its progression.

Association between miR-27a rs895819 polymorphism and breast cancer susceptibility: Evidence based on 6118 cases and 7042 controls.

BACKGROUND: Polymorphism in miR-27a rs895819 has been associated with breast cancer (BC) risk, but studies have reported inconsistent results. This meta-analysis investigated the possible association between miR-27a rs895819 polymorphism and BC risk. METHODS: PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies in English and Chinese. Meta-analyses were performed to examine the association between miR-27a rs895819 and BC susceptibility. RESULTS: A total of 16 case-control studies involving 6118 cases and 7042 controls were included. Analysis using five genetic models suggested no significant association between miR-27a rs895819 polymorphism and BC risk in the total population, or specifically in Asian or Chinese subpopulations. In the Caucasian subpopulation, however, the G-allele and AG genotype at rs895819 were significantly associated with decreased BC risk according to the allelic model (OR 0.90, 95% CI 0.84-0.97, P = .004) and heterozygous model (OR 0.89, 95% CI 0.81-089, P = .02), while the wild-type AA genotype was significantly associated with increased BC risk according to the dominant model (OR 1.13, 95% CI 1.03-1.24, P = .007). CONCLUSION: These results indicate that among Caucasians, the wild-type AA genotype at rs895819 may confer increased susceptibility to BC, while the G-allele and AG genotype may be protective factors. These conclusions should be verified in large, well-designed studies.

Octreotide Reduces Pancreatic Islet Apoptosis and Improves Islet Transplantation Efficiency In Vitro and In Vivo.

The drug octreotide, a somatostatin analog, stimulates the cellular free radical scavenging system and inhibits the release of superoxide anions from monocytes. We hypothesized that octreotide also protects islet ß cell function and improves the survival of transplanted islets by ameliorating the adverse effects of hypoxia and reoxygenation on these cells, thus inhibiting apoptosis. To test this hypothesis, we experimentally induced hypoxia in islet cells in mouse insulinoma Min6 cells. Octreotide treatment mildly but significantly improved cell viability under normoxic and hypoxic conditions. Secreted vascular endothelial growth factor (VEGF) from the Min6 cells was downregulated after octreotide treatment during hypoxia. By contrast, the expression of hypoxia-inducible factor (HIF)-1α was upregulated after octreotide treatment under both normoxic and hypoxic conditions. Octreotide treatment also lowered the apoptotic rate of Min6 cells under hypoxic conditions in vitro. In a mouse transplant model, octreotide improved the post-transplantation efficacy and function of islet grafts. Expression of p53 and Bax in islet grafts was upregulated in the recipients treated with octreotide one day after islet transplantation, and the octreotide-treated group produced significantly less Bax than the control group on days 3 and 7 following transplantation. TUNEL assay further demonstrated a decrease in islet cell apoptosis in the octreotide group on days 1, 3, 7, and 14 after transplantation compared with that of the control group (P < 0.05). No islet cell proliferation was found in the octreotide and control groups on days 1, 3, and 7 following transplantation. However, by day 14, the group treated with octreotide demonstrated significantly higher average cell proliferation rates than the controls did (P < 0.05). Thus, octreotide decreased the apoptosis of islets under hypoxic conditions in vitro and enhanced the efficacy of islet transplantation in vivo. Octreotide has excellent potential for therapeutic applications in islet transplantation and merits further study.

CT-TEE Image Registration for Surgical Navigation of Congenital Heart Disease Based on a Cycle Adversarial Network.

Transesophageal echocardiography (TEE) has become an essential tool in interventional cardiologist's daily toolbox which allows a continuous visualization of the movement of the visceral organ without trauma and the observation of the heartbeat in real time, due to the sensor's location at the esophagus directly behind the heart and it becomes useful for navigation during the surgery. However, TEE images provide very limited data on clear anatomically cardiac structures. Instead, computed tomography (CT) images can provide anatomical information of cardiac structures, which can be used as guidance to interpret TEE images. In this paper, we will focus on how to transfer the anatomical information from CT images to TEE images via registration, which is quite challenging but significant to physicians and clinicians due to the extreme morphological deformation and different appearance between CT and TEE images of the same person. In this paper, we proposed a learning-based method to register cardiac CT images to TEE images. In the proposed method, to reduce the deformation between two images, we introduce the Cycle Generative Adversarial Network (CycleGAN) into our method simulating TEE-like images from CT images to reduce their appearance gap. Then, we perform nongrid registration to align TEE-like images with TEE images. The experimental results on both children' and adults' CT and TEE images show that our proposed method outperforms other compared methods. It is quite noted that reducing the appearance gap between CT and TEE images can benefit physicians and clinicians to get the anatomical information of ROIs in TEE images during the cardiac surgical operation.

Immediate psychological distress in quarantined patients with COVID-19 and its association with peripheral inflammation: A mixed-method study.

Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.

Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients.

OBJECTIVE: This study aimed to investigate the potential parameters associated with imaging progression on chest CT from coronavirus disease 19 (COVID-19) patients. RESULTS: The average age of 273 COVID-19 patients enrolled with imaging progression were older than those without imaging progression (p = 0.006). The white blood cells, platelets, neutrophils and acid glycoprotein were all decreased in imaging progression patients (all p < 0.05), and monocytes were increased (p = 0.025). The parameters including homocysteine, urea, creatinine and serum cystatin C were significantly higher in imaging progression patients (all p < 0.05), while eGFR decreased (p < 0.001). Monocyte-lymphocyte ratio (MLR) was significantly higher in imaging progression patients compared to that in imaging progression-free ones (p < 0.001). Logistic models revealed that age, MLR, homocysteine and period from onset to admission were factors for predicting imaging progression on chest CT at first week from COVID-19 patients (all p < 0.05). CONCLUSION: Age, MLR, homocysteine and period from onset to admission could predict imaging progression on chest CT from COVID-19 patients. METHODS: The primary outcome was imaging progression on chest CT. Baseline parameters were collected at the first day of admission. Imaging manifestations on chest CT were followed-up at (6±1) days.

The Oncogenic Role of CENPA in Hepatocellular Carcinoma Development: Evidence from Bioinformatic Analysis.

OBJECTIVE: This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. METHODS: Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. RESULTS: CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P < 0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P < 0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P = 0.025 and P < 0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P = 0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P < 0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC = 0.683). CONCLUSION: Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.

High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC.

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 (P < .001) and TCGA profile (P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation (P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.