AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?

Immunotherapy has now garnered significant attention as an essential component in cancer therapy during this new era. However, due to immune tolerance, immunosuppressive environment, tumor heterogeneity, immune escape, and other factors, the efficacy of tumor immunotherapy has been limited with its application to very small population size. Energy metabolism not only affects tumor progression but also plays a crucial role in immune escape. Tumor cells are more metabolically active and need more energy and nutrients to maintain their growth, which causes the surrounding immune cells to lack glucose, oxygen, and other nutrients, with the result of decreased immune cell activity and increased immunosuppressive cells. On the other hand, immune cells need to utilize multiple metabolic pathways, for instance, cellular respiration, and oxidative phosphorylation pathways to maintain their activity and normal function. Studies have shown that there is a significant difference in the energy expenditure of immune cells in the resting and activated states. Notably, competitive uptake of glucose is the main cause of impaired T cell function. Conversely, glutamine competition often affects the activation of most immune cells and the transformation of CD4+T cells into inflammatory subtypes. Excessive metabolite lactate often impairs the function of NK cells. Furthermore, the metabolite PGE2 also often inhibits the immune response by inhibiting Th1 differentiation, B cell function, and T cell activation. Additionally, the transformation of tumor-suppressive M1 macrophages into cancer-promoting M2 macrophages is influenced by energy metabolism. Therefore, energy metabolism is a vital factor and component involved in the reconstruction of the tumor immune microenvironment. Noteworthy and vital is that not only does the metabolic program of tumor cells affect the antigen presentation and recognition of immune cells, but also the metabolic program of immune cells affects their own functions, ultimately leading to changes in tumor immune function. Metabolic intervention can not only improve the response of immune cells to tumors, but also increase the immunogenicity of tumors, thereby expanding the population who benefit from immunotherapy. Consequently, identifying metabolic crosstalk molecules that link tumor energy metabolism and immune microenvironment would be a promising anti-tumor immune strategy. AMPK (AMP-activated protein kinase) is a ubiquitous serine/threonine kinase in eukaryotes, serving as the central regulator of metabolic pathways. The sequential activation of AMPK and its associated signaling cascades profoundly impacts the dynamic alterations in tumor cell bioenergetics. By modulating energy metabolism and inflammatory responses, AMPK exerts significant influence on tumor cell development, while also playing a pivotal role in tumor immunotherapy by regulating immune cell activity and function. Furthermore, AMPK-mediated inflammatory response facilitates the recruitment of immune cells to the tumor microenvironment (TIME), thereby impeding tumorigenesis, progression, and metastasis. AMPK, as the link between cell energy homeostasis, tumor bioenergetics, and anti-tumor immunity, will have a significant impact on the treatment and management of oncology patients. That being summarized, the main objective of this review is to pinpoint the efficacy of tumor immunotherapy by regulating the energy metabolism of the tumor immune microenvironment and to provide guidance for the development of new immunotherapy strategies.

Photodynamic therapy improves the outcome of immune checkpoint inhibitors via remodelling anti-tumour immunity in patients with gastric cancer.

BACKGROUND: Photodynamic therapy (PDT) plays an immunoregulatory role in tumours. Here, we conducted a retrospective patient analysis to evaluate the effectiveness of PDT plus immune checkpoint inhibitors (ICIs) in gastric cancer. Further, we performed a dynamic analysis of gastric cancer patients receiving PDT to clarify its effects on anti-tumour immunity. METHODS: Forty ICI-treated patients that received PDT or not were retrospectively analysed. Five patients with gastric adenocarcinoma were enrolled for sample collection before and after PDT. Single-cell RNA/T cell receptor (TCR) sequencing, flow cytometry and histological exanimation were used to analyse the collected specimens. RESULTS: Patients in PDT group had a significantly better OS after ICI treatment than those in No PDT group. Single-cell analysis identified ten cell types in gastric cancer tissues and four sub-populations of T cells. Immune cell infiltration increased in the tumours after PDT and the circular immune cells showed consistent alterations. TCR analysis revealed a specific clonal expansion after PDT in cytotoxic T lymphocytes (CTL), but a constriction in Tregs. The B2M gene is upregulated in tumour cells after PDT and is associated with immune cell infiltration. Several pathways involving the positive regulation of immunity were enriched in tumour cells in the post-PDT group. The interactions following PDT were increased between tumour cells and effector cells but decreased between Tregs and other immune cells. Some co-stimulatory signaling emerged, whereas co-inhibitory signaling disappeared in intercellular communication after PDT. CONCLUSIONS: PDT elicits an anti-tumour response through various mechanisms and is promising as an adjuvant to enhance ICI benefit.

A novel adenosine signalling-based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response.

Reliable prognostic signatures that can reflect the intrinsic characteristics of gastric cancer (GC) are still rare. Here, we developed an adenosine-based prognostic signature and explored its association with the tumour immune in GC patients, aiming at confirming the prognostic value of adenosine-related genes and guiding the GC risk stratification and immunotherapeutic response prediction. We collected adenosine pathway-related genes from STRING websites and manual searching. We enrolled the The Cancer Genome Atlas cohort and four gene expression omnibus cohorts of GC for generating and validating the adenosine pathway-based signature using the Cox regression method. Gene expression in the signature was verified using polymerase chain reaction. We also performed gene set enrichment analysis, immune infiltration assessment and immunotherapy response prediction based on this signature. Our study resulted in a six-gene adenosine signature (GNAS, CXCR4, PPP1R1B, ADCY6, NT5E and NOS3) for risk stratification of GC prognosis, with the highest area under the receiver operating characteristic curve up to 0.767 for predicting 10-year overall survival (OS). In the training cohort, patients with signature-defined high risk had significantly poorer OS than those with low risk (p < .001). Multivariate analysis identified the signature as an independent prognostic factor (hazard ratio 2.863, 95% confidence interval [1.871-4.381], p < .001). These findings were confirmed in four independent cohorts. Expression detection showed that all signature genes were upregulated in both GC tissues and cell lines. Further analysis revealed that the signature-defined high-risk patients were characterised by immunosuppressive states and associated with a poor immunotherapy response. In conclusion, the adenosine pathway-based signature represents a promising risk stratification tool for GC in guiding individualised prognostication and immunotherapy.

Utility of near-infrared fluorescence imaging with indocyanine green in resection of oesophageal squamous cell carcinoma: A literature review and a case report.

BACKGROUND: Surgery remains the main primary treatment for non-advanced oesophageal cancer. Conventional thoracotomy and laparotomy can result in severe trauma, slow recovery, more complications, low quality of life, and reduced survival outcomes. Laparoscopic surgery has reduced the above-mentioned problems. However, some challenges remain associated with this approach, such as lymphadenectomy, anastomotic leakage, and inadequate surgical margins. Near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) in combination with laparoscopic surgery, provides real-time navigation throughout the entire surgical procedure. CASE PRESENTATION: A middle-aged male patient presented to our health centre with progressive dysphagia for > 2 months. Endoscopy and biopsy revealed oesophageal squamous cell carcinoma 34 cm from the incisors (tumour node metastasis classification (TNM) T3N1M0 IIIB). ICG imaging fluorescence laparoscopic surgery was successfully performed to complete the oesophagectomy and oesophageal and tubular stomach anastomosis by accurately locating the lesion, retaining adequate upper and lower margins, visually dissecting the lymph nodes, and testing the anastomotic blood supply. The postoperative TNM stage was T2N0M0 ⅡA. The patient recovered quickly without complications. Postoperative chemotherapy was administered. After three years of follow-up, the patient had no recurrence or complications. CONCLUSIONS: Fluorescence laparoscopy provides an excellent surgical treatment modality for patients with oesophageal cancer.

Photodynamic therapy combined with systemic chemotherapy for unresectable extrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) is a tumor with high invasiveness and poor outcome. The current treatments for unresected ECC are not ideal. Novel strategies are needed to improve the outcomes of patients with unresected ECC. Photodynamic therapy (PDT) plus chemotherapy is one of the promising interventions for ECC patients. We conducted this systematic review to determine the efficacy and safety of PDT plus chemotherapy in unresected ECC patients. METHODS: Databases of PubMed, Cochrane Library, Embase, and Web of science were searched from inception to July 2022. Studies that compared PDT plus chemotherapy to PDT alone or chemotherapy alone in patients with unresected ECC were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for overall survival (OS) and adverse events, respectively. RESULTS: Seven eligible studies were finally included. There are four studies on PDT plus chemotherapy vs. chemotherapy alone and three studies on PDT plus chemotherapy vs. PDT alone. The meta-analysis showed that PDT plus chemotherapy had a significantly better OS than chemotherapy or PDT alone (PDT+chemotherapy vs. chemotherapy alone, HR: 0.69, p = 0.02; PDT+chemotherapy vs. PDT alone, HR:0.36, p<0.01). The occurrence of cholangitis, abscess, and photosensitivity reaction in PDT plus chemotherapy were comparable to either chemotherapy alone or PDT alone (p>0.05). CONCLUSION: The combination of PDT and chemotherapy can improve patient survival for unresected ECC without increased adverse events. It may be a potential standard therapy in the future management of ECC.

Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2-3 clinical trial protocol.

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer. Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer. Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200064280.

Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review.

Photodynamic therapy (PDT) is a non-invasive laser light local treatment that has been utilized in the management of a wide variety of solid tumors. Moreover, the evaluation of efficacy, adverse reactions, the development of new photosensitizers and the latest therapeutic regimens are inseparable from the preliminary exploration in preclinical studies. Therefore, our aim was to better comprehend the characteristics and limitations of these models and to provide a reference for related research. METHODS: We searched the databases, including PubMed, Web of Science and Scopus for the past 25 years of original research articles on the feasibility of PDT in tumor treatment based on preclinical experiments and animal models. We provided insights into inclusion and exclusion criteria and ultimately selected 40 articles for data synthesis. RESULTS: After summarizing and comparing the methods and results of these studies, the experimental model selection map was drawn. There are 7 main preclinical models, which are used for different research objectives according to their characteristics. CONCLUSIONS: Based on this narrative review, preclinical experimental models are crucial to the development and promotion of PDT for tumors. The traditional animal models have some limitations, and the emergence of organoids may be a promising new insight.

Coagulation- and fibrinolysis-related genes for predicting survival and immunotherapy efficacy in colorectal cancer.

Background: Colorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model. Methods: Through online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan-Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot. Results: Five DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC. Conclusion: Overall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.

Pathological complete remission of a locally advanced gastric cancer by neoadjuvant therapy "sandwich" regimen as SOXAP+ fluorescence laparoscopic surgery +SOXAP: Case report.

Gastric cancer is an extremely burdensome and challenging malignant tumor with a high incidence and a high mortality rate, which seriously results in a thorny prognosis for oncology patients. Surgical treatment combined with postoperative adjuvant therapy are currently the most regular methods for the treatment of locally advanced gastric cancer (LAGC), but long-term efficacy is not an ideal outcome. Therefore, herein we report a case of a pathologically confirmed complete remission of LAGC treated by the administration of neoadjuvant therapy combined with fluorescence laparoscopic surgery with more significant long-term survival. With that being mentioned, a 60-year-old man was diagnosed as moderately differentiated gastric antrum adenocarcinoma (T3N1M0). Moreover, after three cycles of SOXAP regimen (Oxaliplatin + S-1+Apatinib + Camrelizumab), and it was found out that the gastric lesion was smaller in size than before, total laparoscopic radical resection of the distal gastric cancer was performed at the time. Furthermore, no tumor cells were seen in gross specimen post operatively, achieving complete remission of the case. In addition, he also underwent three cycles of SOXAP regimen postoperatively. Interestingly and assuredly, he was in good health after an almost 2-year follow up period. These results suggest that this therapeutic regimen is a promising treatment modality for the management of locally advanced gastric cancers.

Photodynamic therapy combined with bimetallic stent in the treatment of gastric cancer with malignant duodenobiliary obstruction: a case report and literature review.

Background: Patients with advanced gastric cancer (GC) often and can develop simultaneous or sequential duodenal and biliary obstructions resulting in reduced quality of life and significantly a reduction in the survival time. However, palliative management, insertion of biliary and duodenal metallic stents can relief these obstructions and has become a feasible and safe therapeutic strategic option. However, the operation of bimetallic stents placement is much more difficult and challenging, for instance, cannot prevent tumor progression and reemerge obstructions. Case Description: This report describes and elucidates a patient with GC who has complicated duodenal and biliary obstructions. In this case, the patient was already at an advanced stage when diagnosed, and the patient had a past medical history of cardiac and pulmonary disorders, with the poor general condition and no chance of undergoing any form of laparoscopic surgery. Furthermore, this patient developed severe symptoms of duodenal and biliary obstructions which have resulted in having nutritional disorders and liver dysfunctions post chemotherapeutic treatment regimens. In order to get rid of those obstructions, endoscopic photodynamic therapy (PDT) combined with duodenal metal stent and biliary metal stent was utilized for palliative treatment. In addition, such combined strategies can provide a longer survival time (11 vs. 7.6 months reported before) and improve the quality of life for patients with GC at an advanced stage. Conclusions: PDT combined with bimetallic stents is a safe and excellent therapeutic strategy for advanced GC which has complicated duodenal and biliary obstructions.

Application of intraoperative photodynamic therapy in patients suspected of recurrence post radical surgery: A single center experience.

BACKGROUND: Difficult to resect tumors may be treated with a combination of radical surgery and photodynamic therapy to try to reduce recurrence. The aim of this single center study is to present results from a combined application of radical surgery with intraoperative PDT for patients with various cancers suspected of high risk for post-operative local recurrence. METHODS: Radical surgery combined with intraoperative PDT was performed in each and every patient under study at different time points from June 2020 to July 2021, and the PDT irradiation time ranged from 10, 20, 25 and 30 min. Hematoporphyrin, as a photo synthesizer, was administered intravenously 48 h before surgery and during the operative period respectively, at a 3 mg/kg dose. In addition, the mean and median survival times for each of these patients were also evaluated. Patient's overall disease-Free Survival (DFS) and survival (OS) were immensely evaluated. RESULTS: 12 patients (33.3% female and 66.7 % male) underwent radical surgery and PDT simultaneously. No photosensitivity events were reported in the included patients, except for one case with a moderate to severe erythema. Intraoperative PDT was tolerated in all included patients without serious liver and kidney damages. As from the time these patients underwent radical surgery and PDT, three mortalities were recorded and the remaining 9 patients had some remarkable outcomes with less or no recurrences. CONCLUSIONS: Intraoperative PDT is a potentially safe therapeutic strategy for various tumor patients who undergo operation. Intraoperative PDT combined with surgery may improve local tumor control but this needs to be tested in a larger patient population.

Photodynamic therapy combined with immunotherapy for an advanced esophageal cancer with an obstruction post metal stent implantation: A case report and literature review.

BACKGROUND: Surgery is the main treatment for resectable esophageal cancer but not for advanced esophageal cancer with distant metastasis. PDT is a therapeutic strategy for dysphagia and select unresectable esophageal cancer, with tremendous advantages of minimal invasiveness and organ-preserving treatment modality. PDT prevents tumor progression and growth by inducing vascular injury and local acute inflammatory responses. Immunotherapy, combined with PDT, may contribute to the efficacy of PDT in the treatment of esophageal cancer and reduce the probability of tumor recurrence. CASE REPORT: A 54-year-old male patient with advanced esophageal cancer was hospitalized in the author's hospital on 20th April 2020, who had been treated with two cycles of chemotherapy at the local hospital but failed. In this case, after metal stent implantation, the patient underwent a remarkable and successful treatment of PDT combined with sintilimab, a PD-1 inhibitor. An additional immune checkpoint inhibitor and chemotherapy offer the opportunity to eliminate residual and invisible tumors. The patient had an excellent prognosis that not only the primary lesion was cured, but also the metastatic lymph nodes were significantly reduced, with no tumor recurrence in the last endoscopic review. CONCLUSION: PDT in combination with immunotherapy is a promising strategy to eliminate primary and metastatic esophageal cancer by generating local and systemic antitumor responses, especially after interventional esophageal stent implantation for relief of obstruction.

A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids.

In the past decade, cancer immunotherapy has achieved great success owing to the unravelling of unknown molecular forces in cancer immunity. However, it is critical that we address the limitations of current immunotherapy, including immune-related adverse events and drug resistance, and further enhance current immunotherapy. Lipids are reported to play important roles in modulating immune responses in cancer. Cancer cells use lipids to support their aggressive behaviour and allow immune evasion. Metabolic reprogramming of cancer cells destroys the equilibrium between lipid anabolism and catabolism, resulting in lipid accumulation within the tumour microenvironment (TME). Consequently, ubiquitous lipids, mainly fatty acids, within the TME can impact the function and phenotype of infiltrating immune cells. Determining the complex roles of lipids and their interactions with the TME will provide new insight for improving anti-tumour immune responses by targeting lipids. Herein, we present a review of recent literature that has demonstrated how lipid metabolism reprogramming occurs in cancer cells and influences cancer immunity. We also summarise the potential for lipid-based clinical translation to modify immune treatment.

Attempt of Real-Time Near-Infrared Fluorescence Imaging Using Indocyanine Green (ICG) in Radical Resection of Gallbladder Cancer: A Case Report.

Surgery is the mainstay of treatment for resectable gallbladder cancer. Near-infrared fluorescence (NIRF) imaging using ICG is an innovation in laparoscopic surgery, which can provide real-time navigation during the whole operation. In this article, we present a 56-year older woman with gallbladder cancer, in which we evaluated the applicability of NIRF imaging using ICG for tumor and biliary tree visualization during the operative procedure of gallbladder cancer. The tumor and biliary tree were clearly visualized by utilizing a green fluorescence dye. The patient was successfully operated radical resection of gallbladder cancer under fluorescence laparoscope, without any complications. According to this case, the utilization of ICG based NIRF imaging is feasible and beneficial in identifying tumors and the biliary tree during radical resection. It can assist in the achievement of a negative margin and lymphatic clearance around the biliary tree. However, further studies are needed to corroborate the results of this case.

Current research developments of patient-derived tumour xenograft models (Review).

Patient-derived tumor xenograft (PDTX) models are established by transferring patient tumors into immunodeficient mice. In these murine models, the characteristics of the primary tumor are retained, including the microenvironment of tumor cell growth and histopathology. Due to this, it has become the most reliable in vivo human cancer model. However, the success rates differ by type of tumor, site of transplantation and tumor aggressiveness. Subcutaneous transplantation is a standard method for PDTX, and subrenal capsule transplantation improves the engraftment rate. Recently, PDTX models are frequently used in the fields of precision medicine, predictive biomarkers, evaluation of drug efficacy and preclinical research on tumor immunotherapeutic drugs. The aim of the present article was to review the establishment, clinical applications and limitations of the PDTX model in tumor research.

Construction and Validation of a Novel Prognostic Signature for Intestinal Type of Gastric Cancer.

BACKGROUND: Intestinal type of gastric cancer (IGC) is the largest subtype of gastric cancer (GC) by Lauren classification. The purpose of this present study was to construct a prognostic signature for IGC patients, based on the high-grade dysplasia (HGD) and IGC tissues, to improve and enhance the prognostic accuracy. METHODS: The microarray datasets and associated clinical characteristics of HGD and IGC were obtained from the Gene Expression Omnibus (GEO) database. Based on the differential expression analysis between HGD and IGC, the prognostic-related differential expression genes (DEGs) were identified in a training set by univariate COX regression analysis. The least absolute shrinkage and selection operator (LASSO) regression was used to construct an optimal prognostic signature. The enrichment analysis was performed by using Gene Set Enrichment Analysis (GSEA). The performance of the nomogram was assessed by the calibration curve and concordance index (C-index). The results were validated by using a testing set. RESULTS: We identified 35 prognostic-related DGEs in the training set. The nine-gene signature was established by LASSO analysis. The nine-gene signature was an independent risk factor in both the training and testing sets. The areas under the curve (AUC) values of receiver operating characteristic (ROC) analysis were 0.733 and 0.700 for the training and testing sets, respectively. In GSEA analysis, the gene expression in high-risk group was enriched in hedgehog signaling, epithelial mesenchymal transition, and angiogenesis. The nomogram for IGC showed good performance with C-index of 0.81 (95% CI: 0.76-0.86) and 0.70 (95% CI: 0.63-0.77) in the training and testing sets, respectively. CONCLUSION: We identified and verified a nine-gene signature for the prognostic prediction of IGC patients, which might identify subgroups of IGC patients and select more suitable therapeutic options.

Intestinal congestion and reperfusion injury: damage caused to the intestinal tract and distal organs.

In clinical practice, intestinal autologous diseases, ailments and organ transplants can cause severe congestive damage to the intestinal tract. However, after the etiological factor is gotten rid of and blood flow is free without any hinderance, further damage to the intestinal wall often occurs, causing other related organ dysfunctions. This ultimately results in intestinal congestion reperfusion injury (ICRI). When the structure and function of the intestine are destroyed, bacteria, metabolites and endotoxins in the intestinal tract perfuse and enter the portal vein through the already compromised intestinal mucosa, to the other organs via the liver. Nevertheless, this gives rise to further aggravation of the injury, and reperfusion injury syndrome occurs. ICRI is a very common complication encountered by clinicians, and its harm is more severe and serious as compared with that caused by ischemia-reperfusion. Quite a few number of studies on ICRI have been reported to date. The exact mechanism of the injury is still idiopathic, and effective treatment strategies are still limited. Based on recent studies, this article is aimed at reviewing the destruction, damage mechanisms resulting from ICRI to the intestinal anatomical sites and distant organs. It is geared towards providing new ideas for the prevention and therapeutic approaches of ICRI.

Risk Assessment and Preventive Treatment for Peritoneal Recurrence Following Radical Resection for Gastric Cancer.

As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.

Prognostic significance of tissue factor in patients with pancreatic cancer: a systematic review protocol.

INTRODUCTION: Pancreatic cancer is a highly aggressive digestive system tumour with poor prognosis. Venous thromboembolism (VTE) is a well-known complication of pancreatic cancer, and tissue factor (TF) contributes to the generation of a hypercoagulable state and thrombotic disease in pancreatic cancer. Several studies showed that an elevated TF level was related to the development of VTE and influenced the survival of patients with pancreatic cancer. Thus, we wish to conduct a systematic review of literature to clarify the prognostic significance of TF in pancreatic cancer. METHODS AND ANALYSIS: Studies comparing the circulating microparticle-associated TF (MP TF) level between patients who had pancreatic cancer with and without VTE will be included to evaluate the roles of TF in VTE development. Studies comparing the survival data between patients with high TF expression and low TF expression will also be included to explore the association of TF expression with patient survival. The outcomes are plasma MP TF level and survival endpoints (overall and progression-free survival), respectively. Primary studies of any type published in English will be included. Two reviewers will search Medline, EMBASE and Cochrane databases from inception to June 2020, retrieve relevant studies, and independently select the literatures and extract data from the included studies. The quality of each included study will be assessed by the Newcastle-Ottawa Scale score. The HR and 95% CI of each study will be pooled for survival outcome, and the standardised mean difference (SMD) with 95% CIs will be used for continuous outcomes. If meta-analysis is inappropriate, the result will only be reported qualitatively. Subgroup and sensitivity analyses will be considered to identify sources of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence of this systematic review. ETHICS AND DISSEMINATION: There are no concerning ethical issues. The results will be published. PROSPERO REGISTRATION NUMBER: CRD42019133665.

Silicate-based bioceramic scaffolds for dual-lineage regeneration of osteochondral defect.

Osteochondral defects are most commonly characterized by damages to both cartilage and bone tissues as a result of serious traumas or physical diseases; because these two tissues have their own unique biological properties, developing a single monophasic scaffold that can concurrently regenerate these two specific lineages becomes a challenge. To address this concern, a silicon-based bioceramic (SiCP) scaffold was fabricated. The efficiency and underlying mechanisms of SiCP for osteochondral defect regeneration were investigated. At 8 and 16 weeks post-implantation in a rabbit model of osteochondral defect, gross morphology, histological, and micro-CT images showed that SiCP scaffolds distinctly promoted subchondral bone and cartilage regeneration when compared to calcium-phosphate based bioceramics (CP) scaffolds without silicon. In vitro, SiCP was also shown to promote bone marrow stem cells (BMSC) osteogenesis (ALP, RUNX2, OCN) and help maintain chondrocytes phenotype (Acan, Sox9, Col2a1), validated by qPCR, western blot, and RNA-sequencing (RNA-seq). Additionally, the descriptive analysis of RNA-seq using Gene Ontology (GO) and KEGG pathway analysis revealed biological processes related to cartilage and bone development and extracellular matrices in chondrocytes, as well as related to early osteogenesis in BMSC, indicating that Si ions play an important role in the regeneration of both tissues. Conclusively, the development of silicon-based bioceramic scaffolds may be a promising approach for osteochondral defect regeneration due to their unique dual-lineage bioactivity.