Clinical application of the retrograde track method in reopening dysfunctional biliary stents.

Background: Biliary stent dysfunction is challenging to treat in clinic. The retrograde track method (RTM) has a promising clinical application in the reopening of dysfunctional biliary stents. This study aimed to evaluate the clinical value of the RTM in reopening dysfunctional biliary stents. Methods: From February 2013 to January 2020, 151 patients underwent percutaneous transhepatic biliary interventional procedures for reopening dysfunctional biliary stents at the First Affiliated Hospital of Zhengzhou University, and 25 patients (12 females, 13 males; mean age 63.12 years old) underwent the RTM after anterograde reopening dysfunction biliary stent failure. Technical success, clinical success, irradiation dose, procedure time, complications, and overall survival (OS) were recorded, and levels of total bilirubin (TBIL), direct bilirubin (DB), alanine aminotransferase (ALT), albumin (ALB), and carbohydrate antigen-199 (CA-199) were compared before treatment and 1 month after treatment. Results: The technical and clinical success rates were 100% and 96%, respectively, and the irradiation dose and procedure times were 774.07±330.80 mGy and 45.16±9.48 min, respectively. Two patients (8%) experienced major complications. The median OS was 10.73 months [95% confidence interval (CI): 9.37-12.09]. Compared with pretreatment values, the mean levels at 1 month after RTM administration for TBIL (189.47±59.20 vs. 44.65±16.12 µmol/L), DB (144.21±55.83 vs. 27.95±13.86 µmol/L), ALT (89.62±30.85 vs. 49.44±14.25 U/L), and CA-199 (584.59±269.82 vs. 176.76±100.68 U/mL) showed significant decreases, while that of ALB (36.32±2.05 vs. 40.22±1.95 g/L) showed a significant increase (all P values <0.05). Conclusions: RTM is an effective alternative treatment method when anterograde reopening of a dysfunctional biliary stent occurs.

N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1.

BACKGROUND: Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. METHODS: CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. RESULTS: Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. CONCLUSIONS: Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.

A novel technique to remove migrated esophageal stent under fluoroscopy.

PURPOSE: To evaluate the efficacy and safety of a novel technique for removal of migrated esophageal stent (MES) under fluoroscopy. METHODS: From January 2009 to April 2023, 793 patients with a dysphagia score of 3-4 underwent esophageal stenting at our center, and 25 patients (mean age: 70.06 years old; male/female: 15/10) underwent stent removal using "loop method" under fluoroscopy. The primary outcomes were technical success and complications. The secondary outcomes were procedure time, radiation exposure, biochemical indicators [white blood cell (WBC), hemoglobin (Hb), platelet (PLT), albumin (ALB), alanine transaminase (ALT), total bilirubin (TB), urea nitrogen (UN) and C-reactive protein] of pre- and post-treatment at 2 weeks. RESULTS: Technical success was 100% without major complications. The mean procedure time was (39.44 ± 9.28) minutes, which showed no statistical significance between benign (n = 5) and malignant (n = 20) group [(42.40 ± 8.85) vs (38.71 ± 9.46) mins, p > 0.05]. The mean radiation exposure was (332.88 ± 261.47) mGy, which showed no statistical significance between benign and malignant group [(360.74 ± 231.43) vs (325.92 ± 273.54) mGy, p > 0.05]. Pre- and post-procedure Hb [(114.46 ± 11.96) vs. (117.57 ± 13.12) g/L] and ALB [(42.26 ± 3.39) vs. (44.12 ± 3.77) g/L] showed significant difference (p < 0.05), while WBC, PLT, CRP, and ALT showed no significance (p > 0.05). CONCLUSION: Fluoroscopy-guided "Loop method" for MES removal is an effective and safe alternative technique.

GC-CDSS: Personalized gastric cancer treatment recommendations system based on knowledge graph.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, posing a serious threat to human health. Currently, gastric cancer treatment strategies emphasize a multidisciplinary team (MDT) consultation approach. However, there are numerous treatment guidelines and insights from clinical trials. The application of AI-based Clinical Decision Support System (CDSS) in tumor diagnosis and screening is increasing rapidly. OBJECTIVE: The purpose of this study is to (1) summarize the treatment decision process for GC according to the treatment guidelines in China, and then create a knowledge graph (KG) for GC, (2) based on aforementioned KG, built a CDSS and conducted an initial feasibility evaluation for the current system. METHODS: Firstly, we summarized the decision-making process for treatment of GC. Then, we extracted relevant decision nodes and relationships and utilized Neo4j to create the KG. After obtaining the initial node features for building the graph embedding model, graph embedding algorithm, such as Node2Vec and GraphSAGE, were used to construct the GC-CDSS. At last, a retrospective cohort study was used to compare the consistency between GC-CDSS and MDT in treatment decision making. RESULTS: In current study, we introduce a GC-CDSS, which is constructed based on Chinese GC treatment guidelines knowledge graph (KG). In the KG, we define four types of nodes and four types of relationships, and it comprise a total of 207 nodes and 300 relationships. Regarding GC-CDSS, the system is capable of providing dynamic and personalized diagnostic and treatment recommendations based on the patient's condition. Furthermore, a retrospective cohort study is conducted to compare GC-CDSS recommendations with those of the MDT group, the overall consistency rate of treatment recommendations between the auxiliary decision system and MDT team is 92.96%. CONCLUSIONS: We construct a GC treatment support system, GC-CDSS, based on KG. The GC-CDSS may help oncologists make treatment decisions more efficient and promote standardization in primary healthcare settings.

Comprehensive multi-omics analysis and experimental verification reveal PFDN5 is a novel prognostic and therapeutic biomarker for gastric cancer.

Prefoldin Subunit 5 (PFDN5) plays a critical role as a member of the prefoldins (PFDNs) in maintaining a finely tuned equilibrium between protein production and degradation. However, there has been no comprehensive analysis specifically focused on PFDN5 thus far. Here, a comprehensive multi-omics (transcriptomics, genomics, and proteomics) analysis, systematic molecular biology experiments (in vitro and in vivo), transcriptome sequencing and PCR Array were performed for identifying the value of PFDN5 in pan-cancer, especially in Gastric Cancer (GC). We found PFDN5 had the potential to serve as a prognostic and therapeutic biomarker in GC. And PFDN5 could promote the proliferation of GC cells, primarily by affecting the cell cycle, cell death and immune process etc. These findings provide novel insights into the molecular mechanisms and precise treatments of in GC.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest.

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

Clinical application of intravascular forceps biopsy in the diagnosis of vascular obstructive diseases: a pilot study.

Background: The sampling of vascular obstruction diseases remains a challenge in clinical practice. This retrospective study aimed to evaluate the feasibility, accuracy, and safety of intravascular forceps biopsy (IVFB) for the diagnosis of vascular obstructive diseases. Methods: From January 2015 to January 2022, of the total of 35 patients who underwent IVFB (21 male, 14 female; mean age 60±11 years; range, 39-81 years), 32 (91.4%) did so during interventional planned revascularization procedures and 3 (8.6%) did so due so due to inaccessible or failed percutaneous access. The outcomes of technical success, biopsy times, patient radiation dose (PRD), complications, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate (AR) were analyzed. Results: The technical success of IVFB was 100%. The median number of biopsies taken per biopsy session and PRD were 4.0 (range, 3-6) and 712.6 mGy (range, 383.4-1,450.8), respectively. The sensitivity, specificity, PPV, NPV, and AR of IVFB were 87.5% (21/24), 100% (11/11), 100% (21/21), 78.6% (11/14), and 91.4% (32/35), respectively. There were no complications related to IVFB. Conclusions: IVFB is a technically feasible and safe technique with good diagnostic value. The procedure should be considered in patients who are not suitable for percutaneous access, show indistinct imaging characteristics, or are scheduled to undergo revascularization procedure.

Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis.

Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy. Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4+ T cells. Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4+ T cells and a negative correlation between ADAMTS13 and CD4+ T cells. Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC.

Impact of Cuproptosis-related markers on clinical status, tumor immune microenvironment and immunotherapy in colorectal cancer: A multi-omic analysis.

Background: Cuproptosis, a novel identified cell death form induced by copper, is characterized by aggregation of lipoylated mitochondrial enzymes and the destabilization of Fe-S cluster proteins. However, the function and potential clinical value of cuproptosis and cuproptosis-related biomarkers in colorectal cancer (CRC) remain largely unknown. Methods: A comprehensive multi-omics (transcriptomics, genomics, and single-cell transcriptome) analysis was performed for identifying the influence of 16 cuproptosis-related markers on clinical status, molecular functions and tumor microenvironment (TME) in CRC. A novel cuproptosis-related scoring system (CuproScore) based on cuproptosis-related markers was also constructed to predict the prognosis of CRC individuals, TME and the response to immunotherapy. In addition, our transcriptome cohort of 15 paired CRC tissue, tissue-array, and various assays in 4 kinds of CRC cell lines in vitro were applied for verification. Results: Cuproptosis-related markers were closely associated with both clinical prognosis and molecular functions. And the cuproptosis-related molecular phenotypes and scoring system (CuproScore) could distinguish and predict the prognosis of CRC patients, TME, and the response to immunotherapy in both public and our transcriptome cohorts. Besides, the expression, function and clinical significance of these markers were also checked and analyzed in CRC cell lines and CRC tissues in our own cohorts. Conclusions: In conclusion, we indicated that cuproptosis and CPRMs played a significant role in CRC progression and in modeling the TME. Inducing cuproptosis may be a useful tool for tumor therapy in the future.

TACE sequential MWA guided by cone-beam computed tomography in the treatment of small hepatocellular carcinoma under the hepatic dome.

PURPOSE: An assessment is being conducted to determine the safety and effectiveness of using Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) sequentially to treat small hepatocellular carcinomas (HCCs) located in the hepatic dome. MATERIALS AND METHODS: Fifty-three patients with small HCCs in the hepatic dome who underwent TACE combined with simultaneous CBCT-guided MWA were studied. Inclusion criteria were a single HCCs ≤ 5.0 cm or a maximum of three. The safety and interventional-related complications were monitored, and local tumor progression (LTP), overall survival (OS), and prognostic factors for LTP/OS were evaluated. RESULTS: The procedures were successfully accomplished in all patients. According to Common Terminology Criteria for Adverse Events (CTCAE), adverse reactions and complications are mainly Grade 1 or 2 (mild symptoms, no or local/noninvasive intervention indicated). Liver and kidney function and alpha-fetoprotein (AFP) levels remained within a reasonable range after 4 weeks of treatment (both p < 0.001). The mean LTP was 44.406 months (95% CI: 39.429, 49.383) and the mean OS rate was 55.157 months (95% CI: 52.559, 57.754). The combination treatment achieved 1-, 3-, and 5-year LTP rates of 92.5%, 69.6%, and 34.5%, respectively; and 1-, 3-, and 5-year OS rates of 100.0%, 88.4%, and 70.2%, respectively. Results from both univariate and multivariate Cox regression analyses showed that the tumor diameter (< 3 cm) and the distance to the hepatic dome (≥ 5 mm, < 10 mm) had a significant impact on the patient's LTP and OS, and were related to better survival. CONCLUSION: CBCT-guided TACE combined with simultaneous MWA was a safe and successful treatment of HCCs located under the hepatic dome.

Polyamine metabolism patterns characterized tumor microenvironment, prognosis, and response to immunotherapy in colorectal cancer.

BACKGROUND: Changes in Polyamine metabolism (PAM) have been shown to establish a suppressive tumor microenvironment (TME) and substantially influence the progression of cancer in the recent studies. However, newly emerging data have still been unable to fully illuminate the specific effects of PAM in human cancers. Here, we analyzed the expression profiles and clinical relevance of PAM genes in colorectal cancer (CRC). METHODS: Based on unsupervised consensus clustering and principal component analysis (PCA) algorithm, we designed a scoring model to evaluate the prognosis of CRC patients and characterize the TME immune profiles, with related independent immunohistochemical validation cohort. Through comparative profiling of cell communities defined by single cell sequencing data, we identified the distinct characteristics of polyamine metabolism in the TME of CRC. RESULTS: Three PAM patterns with distinct prognosis and TME features were recognized from 1224 CRC samples. Moreover, CRC patients could be divided into high- and low-PAMscore subgroups by PCA-based scoring system. High PAMscore subgroup were associated to more advanced stage, higher infiltration level of immunosuppressive cells, and unfavorable prognosis. These results were also validated in CRC samples from other public CRC datasets and our own cohort, which suggested PAM genes were ideal biomarkers for predicting CRC prognosis. Notably, PAMscore also corelated with microsatellite instability-high (MSI-H) status, higher tumor mutational burden (TMB), and increased immune checkpoint gene expression, implying a potential role of PAM genes in regulating response to immunotherapy. To further confirm above results, we demonstrated a high-resolution landscape of TME and cell-cell communication network in different PAM patterns using single cell sequencing data and found that polyamine metabolism affected the communication between cancer cells and several immune cells such as T cells, B cells and myeloid cells. CONCLUSION: In total, our findings highlighted the significance of polyamine metabolism in shaping the TME and predicting the prognosis of CRC patients, providing novel strategies for immunotherapy and the targeting polyamine metabolites.

Percutaneous transhepatic intraluminal forceps biopsy for patients with biliary stricture after endoscopic retrograde approach failure: a retrospective study.

Background: The etiological diagnosis of biliary stricture remains a clinical challenge. Currently, endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary biopsy is the most commonly used technique. This retrospective study aimed to evaluate the clinical value of percutaneous transhepatic intraluminal forceps biopsy (TIFB) in patients with biliary stricture after ERCP failure. Methods: The clinical data of 240 consecutive patients with biliary strictures who sought further etiologic diagnosis at our center between April 2014 and January 2020 were collected. After the exclusion of 197 patients who underwent ERCP-guided biopsy, 43 patients who received TIFB after ERCP failure were included in the study. The primary outcomes were technical success, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Secondary outcomes included procedure duration, radiation exposure, liver function [total bilirubin (TB), direct bilirubin (DB), γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] preoperatively and at 2 weeks postoperatively, and complications. Results: The technical success rate of TIFB was 100%. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of TIFB were 82.35%, 100%, 86.05%, 100%, and 60%, respectively. The accuracy of TIFB was significantly higher for cases with suspicious biliary tract invasion on imaging and intrabiliary malignant origin than it did for cases with no suspicious biliary tract invasion on imaging or extrabiliary malignant origin (P=0.007 and P=0.003, respectively). Only intrabiliary malignant origin (P=0.02) was an independent contributing factor for a true positive result in TIFB diagnosis. The mean procedure duration was 19.3 minutes and the mean radiation exposure was 315.6 mGy. All liver function markers were significantly reduced after 2 weeks (all P<0.001). Three (6.97%) complications occurred, including 1 (2.33%) case of cholangitis and 2 (4.65%) cases of hemobilia. Conclusions: Percutaneous TIFB is an effective method with high sensitivity and accuracy for the etiological diagnosis of biliary stricture after ERCP failure.

Roles and mechanisms of tumour-infiltrating B cells in human cancer: a new force in immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 have emerged as a revolutionary treatment strategy for human cancer patients. However, as the response rate to ICI therapy varies widely among different types of tumours, we are beginning to gain insight into the mechanisms as well as biomarkers of therapeutic response and resistance. Numerous studies have highlighted the dominant role of cytotoxic T cells in determining the treatment response to ICIs. Empowered by recent technical advances, such as single-cell sequencing, tumour-infiltrating B cells have been identified as a key regulator in several solid tumours by affecting tumour progression and the response to ICIs. In the current review, we summarized recent advances regarding the role and underlying mechanisms of B cells in human cancer and therapy. Some studies have shown that B-cell abundance in cancer is positively associated with favourable clinical outcomes, while others have indicated that they are tumour-promoting, implying that the biological function of B cells is a complex landscape. The molecular mechanisms involved multiple aspects of the functions of B cells, including the activation of CD8+ T cells, the secretion of antibodies and cytokines, and the facilitation of the antigen presentation process. In addition, other crucial mechanisms, such as the functions of regulatory B cells (Bregs) and plasma cells, are discussed. Here, by summarizing the advances and dilemmas of recent studies, we depicted the current landscape of B cells in cancers and paved the way for future research in this field.

Application of a highly simulated and adaptable training system in the laparoscopic training course for surgical residents: Experience from a high-volume teaching hospital in China.

Objective: To explore the effectiveness, feasibility, and training effect of a highly simulated and adaptable laparoscopic training system in the advanced integrated two-stage laparoscopic simulation training course for surgical residents. Methods: This study prospectively took the surgical residents who received the advanced integrated two-stage laparoscopic simulation training course in our hospital from December 2019 to December 2021 as the research objects. In the stage one course, the trainees are randomly distributed into the dry simulation system group and Darwin laparoscopic training system group. The subjective assessment results of the trainees from the two groups are collected by questionnaires, and the simulation assessment results of the two groups are evaluated in a unified, objective, and standardized assessment form. The pre-course and post-course questionnaires were used to evaluate the feasibility and effectiveness of the Darwin system in the stage two course. Results: A total of 62 trainees completed the stage one and stage two courses. In the stage one course, the trainees were randomly distributed into the dry simulation trainer group (N = 19) and the Darwin group (N = 43). The results of the subjective assessment questionnaire showed that compared with the dry simulator group, the students in the Darwin group had higher subjective scores (P < 0.05). The objective assessment results for the 3 modules of "One Track Transfer", "One Tunnel Pass" and "High and Low Pillars" in the Darwin group were significantly better than those in the dry simulator group (P < 0.05). The trainees who received the stage two course completed the questionnaires before and after the course. The results showed that compared with pre-course evaluation, "basic theoretical knowledge of laparoscopy", "basic skills of laparoscopy", "laparoscopic suture technique" and "camera-holding technique" were significantly improved after training (P < 0.05). Conclusion: The highly simulated and adaptable laparoscopic training system is effective and feasible in the advanced integrated two-stage laparoscopic simulation training course for surgical residents.

PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway.

Objective: Colorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into. Methods: The expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo. Results: PKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT. Conclusion: The increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.

An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review.

Malignant tumors are the second leading cause of death worldwide. This is a public health concern that negatively impacts human health and poses a threat to the safety of life. Although there are several treatment approaches for malignant tumors, surgical resection remains the primary and direct treatment for malignant solid tumors. Anesthesia is an integral part of the operation process. Different anesthesia techniques and drugs have different effects on the operation and the postoperative prognosis. Propofol is an intravenous anesthetic that is commonly used in surgery. A substantial number of studies have shown that propofol participates in the pathophysiological process related to malignant tumors and affects the occurrence and development of malignant tumors, including anti-tumor effect, pro-tumor effect, and regulation of drug resistance. Propofol can also reshape the tumor microenvironment, including anti-angiogenesis, regulation of immunity, reduction of inflammation and remodeling of the extracellular matrix. Furthermore, most clinical studies have also indicated that propofol may contribute to a better postoperative outcome in some malignant tumor surgeries. Therefore, the author reviewed the chemical properties, pharmacokinetics, clinical application and limitations, mechanism of influencing the biological characteristics of malignant tumors and reshaping the tumor microenvironment, studies of propofol in animal tumor models and its relationship with postoperative prognosis of propofol in combination with the relevant literature in recent years, to lay a foundation for further study on the correlation between propofol and malignant tumor and provide theoretical guidance for the selection of anesthetics in malignant tumor surgery.

Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation.

Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation. Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC. Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs. Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.

A Novel Defined RAS-Related Gene Signature for Predicting the Prognosis and Characterization of Biological Function in Osteosarcoma.

Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents with a high incidence and poor prognosis. Activation of the RAS pathway promotes progression and metastasis of osteosarcoma. RAS has been studied in many different tumors; however, the prognostic value of RAS-associated genes in OS remains unclear. On this basis, we investigated the RAS-related gene signature and explored the intrinsic biological features of OS. Methods: We obtained RNA transcriptome sequencing data and clinical information of osteosarcoma patients from the TARGET database. RAS pathway-related genes were obtained from the KEGG pathway database. Molecular subgroups and risk models were developed using consensus clustering and least absolute shrinkage and selection operator (LASSO) regression, respectively. ESTIMATE algorithm and ssGSEA analysis were used to assess the tumor microenvironment and immune penetrance between the two groups. A comprehensive review of gene ontology (GO) and KEGG analyses revealed inherent biological functional differences between the two groups. Results: The consistent clustering showed stratification of osteosarcoma patients into two subtypes based on RAS-associated genes and provided a robust prediction of prognosis. A risk model further confirmed that RAS-related genes are the best prognostic indicators for OS patients. GO analysis showed that GDP/GTP binding, focal adhesion, cytoskeletal motor activity, and cell-matrix junctions were associated with the RAS-related model group. Furthermore, RAS signaling in osteosarcoma based on KEGG analysis was significantly associated with cancer progression, with immune function and tumor microenvironment particularly affected. Conclusion: We constructed a prognostic model founded on RAS-related gene and demonstrated its predictive ability. Then, furtherly exploration of the molecular mechanisms and immune characteristics proved the role of RAS-related gene in the dysregulation in OS.