Different Expression Profiles of Exosomal circRNAs from Apheresis Platelets during Storage.

Introduction: Bioactive substances of stored platelets change during the stored periods. Exosomes are reported to be increased during platelet storage. Circular RNAs (circRNAs) are one of the main components in exosomes. It is the purpose of this study to investigate the different expression of exosomal circRNAs during storage. Methods: Apheresis platelets were collected from 7 healthy volunteers and stored in platelet storage bags for 1 day or 5 days. We isolated exosomes by ultracentrifugation and characterized exosomes by transmission electron microscopy, nano-flow cytometry, and Western blot. We conducted microarray analysis to detect changes in the exosomal circRNAs from apheresis platelets during storage, and qRT-PCR to validate their expressions. To analyze the competing endogenous RNA (ceRNA) of circRNAs, microRNAs (miRNAs) targets were predicted based on interactions of circRNAs/miRNAs and miRNAs/mRNAs, using TargetScan and miRanda. A ceRNA network was constructed by Cytoscape. The targeted mRNAs were performed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis by the DAVID. Results: Microarray analysis revealed that 61 differentially expressed circRNAs between day 1 and day 5. Thirty-one circRNAs of these are upregulated, while 30 circRNAs are downregulated. A ceRNA visualized network includes 9 circRNAs, 48 miRNAs, and 117 mRNAs. There were 117 mRNAs enriched in 203 GO terms and 9 KEGG pathways based on the GO and KEGG pathway enrichment analyses. Conclusion: We identified 61 dysregulated exosomal circRNAs from apheresis platelets during storage. The study provided insights into the underlying mechanisms of platelet storage lesion.

Comparison of transfusion rates between robotic- and video-assisted lobectomy: a propensity score matching analysis.

The objective is to compare the perioperative blood transfusion rate and postoperative complications between robot-assisted surgery and thoracoscopic surgery in lung cancer patients. This is a single-center retrospective study. Patients underwent lung cancer minimally invasive resection at Fujian Cancer Hospital from April 1, 2022, to April 30, 2023, were enrolled in this study. Patients were divided into robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) groups according to the surgical methods. Data, including demographics, clinic variables, and endpoint outcomes were collected from the electronic medical record. Propensity score matching (PSM) was performed to analyze the baseline data of patients. The RAL group and the VAL group were matched 1:1. Then, the blood transfusion rates and short-term outcomes of the two groups were compared. A logistic regression was performed to analyze the independent risk factors of perioperative blood transfusion. A total of 558 patients were enrolled in this study. 166 of 558 patients were divided into the RAL group, and 392 patients were into the VAL group. A total of 118 patients were selected and analyzed following propensity score matching. After PSM, there was no difference in perioperative transfusion rates, including RBC transfusion and frozen plasma transfusion, between the VAL and RAL groups (P > 0.05). The RAL group had fewer days of drainage tubes (P = 0.036). There was no difference in other short-term outcomes, including the volume of thoracic drainage, the volume of intraoperative blood loss, the length of hospitalization, and the rate of postoperative pulmonary infection (P > 0.05). Volume of intraoperative blood loss, volume of thoracic drainage, and preoperative hemoglobin were independent risk factors of perioperative red blood cell or frozen plasma transfusion; however, RAL or VAL was not. The study showed that the rates of perioperative blood transfusion were comparable between RAL and VAL. RAL is superior for patient recovery in terms of short-term outcomes.

Mechanism of regulation of the Helicobacter pylori Cagß ATPase by CagZ.

The transport of the CagA effector into gastric epithelial cells by the Cag Type IV secretion system (Cag T4SS) of Helicobacter pylori (H. pylori) is critical for pathogenesis. CagA is recruited to Cag T4SS by the Cagß ATPase. CagZ, a unique protein in H. pylori, regulates Cagß-mediated CagA transport, but the underlying mechanisms remain unclear. Here we report the crystal structure of the cytosolic region of Cagß, showing a typical ring-like hexameric assembly. The central channel of the ring is narrow, suggesting that CagA must unfold for transport through the channel. Our structure of CagZ in complex with the all-alpha domain (AAD) of Cagß shows that CagZ adopts an overall U-shape and tightly embraces Cagß. This binding mode of CagZ is incompatible with the formation of the Cagß hexamer essential for the ATPase activity. CagZ therefore inhibits Cagß by trapping it in the monomeric state. Based on these findings, we propose a refined model for the transport of CagA by Cagß.

Hsa_circ_0040809 and hsa_circ_0000467 promote colorectal cancer cells progression and construction of a circRNA-miRNA-mRNA network.

Objective: Circular RNAs (circRNAs) have been demonstrated to be closely involved in colorectal cancer (CRC) pathogenesis and metastasis. More potential biomarkers are needed to be searched for colorectal cancer (CRC) diagnosis and treatment. The objective of this study is to seek differentially expressed circRNAs (DEcircRNAs), test their roles in CRC and construct a potential competing endogenous RNA (ceRNA) network. Methods: CircRNA microarrays were obtained from Gene Expression Omnibus, and differential expression was analyzed by R software. The relative expressions of DEcircRNAs were confirmed in CRC tissues and cell lines by qRT-PCR. MTs and Transwell experiments were performed for detecting the roles of circRNAs on CRC cell proliferation and migration, respectively. Targeted miRNAs of circRNAs and targeted mRNAs of miRNAs were predicted and screened by bioinformatics methods. A ceRNA network of DEcircRNAs was constructed by Cytoscape. To further verify the potential ceRNA network, the expressions of miRNAs and mRNAs in knockdown of DEcircRNAs CRC cells were detected by qRT-PCR. Results: Two DEcircRNAs (hsa_circ_0040809 and hsa_circ_0000467) were identified and validated in CRC tissues and cell lines. The results of MTs and Transwell experiments showed that hsa_circ_0040809 and hsa_circ_0000467 promoted CRC proliferation and migration. Bioinformatics analysis screened 3 miRNAs (miR-326, miR-330-5p, and miR-330-3p) and 2 mRNAs (FADS1 and RUNX1), and a ceRNA network was constructed. In knockdown of hsa_circ_0040809 HCT-116 cells, the expression of miR-330-3p was significantly upregulated, while RUNX1 was significantly downregulated. In knockdown of hsa_circ_0000467 HCT-116 cells, the expressions of miR-326 and miR-330-3p were upregulated, while FADS1was downregulated. Conclusion: We found that hsa_circ_0040809 and hsa_circ_0000467 were upregulated in CRC tissues and cell lines, and promoted CRC cell progression. A circRNA-miRNA-mRNA network based on hsa_circ_0040809 and hsa_circ_0000467 was constructed.

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study.

Objective: This study analyzed metabolic factors associated with lymphovascular space invasion (LVSI) and compared the difference between type 1 and type 2 endometrial cancer (EC). Methods: Four hundred patients primarily diagnosed with EC who underwent hysterectomy with pathological results at Fujian Medical University Cancer Hospital from January 2019 to January 2021 were included. Demographic variable data were collected as well as pathological results. Laboratory evaluations included fasting blood glucose (FBG), serum cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (Apo A) and apolipoprotein B (Apo B). Characterization of binary logistic regression models was used to test the odds ratios (ORs) between LVSI and its metabolic parameters with different subtypes of EC. Results: The results indicated that CA125, ROMA, Ki67 score, FBG and TC were higher in EC patients with LVSI (all p<0.05). Negative ER and PR expression was positively associated with LVSI (P<0.05). CA125, ROMA, FBG, TC and ER were found to be independent risk factors for LVSI. CA125, ROMA and FBG were significantly elevated in type 1 EC patients with LVSI compared with those without LVSI (all p<0.05). TC and Ki67 scores were much higher in type 2 EC patients with vs without LVSI (all p<0.05). Negative PR expression was positively related to both type 1 and type 2 EC patients with LVSI. Consequently, CA125, ROMA, FBG and Apo B were found to be independent risk factors for LVSI in type 1 EC, and TC was found to be an independent risk factor for LVSI in type 2 EC. Conclusion: FBG and TC were both independent risk factors for LVSI in EC. FBG and Apo B were independent risk factors for LVSI in type 1 EC. TC was an independent risk factor for LVSI in type 2 EC.

Mechanisms of thrombosis and research progress on targeted antithrombotic drugs.

Globally, the incidence of thromboembolic diseases has increased in recent years, accompanied by an increase in patient mortality. Currently, several targeting delivery strategies have been developed to treat thromboembolic diseases. In this review, we discuss the mechanisms of thrombolysis and current anticoagulant drugs, particularly those with targeting capability, highlighting advances in the accurate treatment of thrombolysis with fewer adverse effects. Such approaches include magnetic drug-loading systems combined with molecular imaging to recanalize blood vessels and systems based on chimeric Arg-Gly-Asp (RGD) sequences that can target platelet glycoprotein receptor. With such progress in targeted antithrombotic drugs, targeted thrombolysis treatment shows significant potential benefit for patients.

Identification of downregulated circRNAs from tissue and plasma of patients with gastric cancer and construction of a circRNA-miRNA-mRNA network.

The connection between circular RNAs (circRNAs) and gastric cancer has been reported widely in recent years. However, previous studies have focused mainly on circRNAs from gastric cancer tissue. The objectives of the present study were to detect dysregulated circRNAs from both tissue and plasma of patients with gastric cancer and to explore their potential roles in the pathogenesis of gastric cancer. Expression profiles of circRNAs were obtained from the Gene Expression Omnibus (GEO) and analyzed using the GEO2R tool to identify differential expressed circRNAs. The significance threshold was set as |log2 (fold change)| > 2 and adjusted P < .05. The microRNA (miRNA) binding sites of the differentially expressed circRNAs were predicted using the Circular RNA Interactome web tool. TargetScan and the miRNet database were used to predict the miRNA target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using Database for Annotation Visualization and Integrated Discovery. Hub genes were identified and a network was constructed with Cytoscape. The overall survival rates for the selected miRNAs and messenger RNAs were evaluated by Kaplan-Meier Plotter. A total of three downregulated circRNAs (hsa_circ_0001190, hsa_circ_0036287, and hsa_circ_0048607) were identified in this study. Six miRNAs and eight hub genes met the significance criteria and were selected for further analysis. A circRNA-miRNA-hub gene network was constructed based on three circRNAs, six miRNAs, and eight hub genes. Evaluation of overall survival rates for the hub genes showed that low expression levels of GADD45A, PPP1CB, PJA2, and KLF2 were associated with poor overall survival. This study identified potential novel plasma circRNA biomarkers and provides insights into the underlying mechanisms of gastric cancer pathogenesis.

Chemotherapy-induced thrombocytopenia and platelet transfusion in patients with diffuse large B-cell lymphoma.

BACKGROUND: Currently, the risk factors associated with chemotherapy-induced thrombocytopenia (CIT) in patients with diffuse large B-cell lymphoma (DLBCL) are still undefined. Our study aimed to analyze the effects of risk factors on thrombocytopenia and to identify the threshold for infusion platelets of CIT patients who have received platelet transfusions. METHODS: We conducted a retrospective analysis of 523 patients with DLBCL from 2011 to 2013. The clinical and demographic parameters were extracted, and the risk factors associated with CIT were analyzed. The threshold for platelet transfusions in DLBCL patients with a central venous catheter (CVC) was evaluated. RESULTS: A total of 227 (43.4%) DLBCL patients had thrombocytopenia, and 63 (12.0%) had thrombocytopenia without concomitant cytopenia. We found that the choice of chemotherapy regimen was positively correlated with thrombocytopenia (P<0.001). The chemotherapy regimens most likely to result in thrombocytopenia were dexamethasone, cytarabine, cisplatin (DHAP) (92.3%), isophosphamide, carboplatin, etoposide (ICE) (89.7%), gemcitabine, dexamethasone, cisplatin (GDP) (89.7%), gemcitabine, and oxaliplatin (Gemox) (69.0%). In addition to these, high lactate dehydrogenase (LDH) (P=0.004) and Ann Arbor stage III/IV (P=0.024) were determined to be risk factors leading to thrombocytopenia. Forty patients (17.6%) had transfused platelets, and all of them were placed in the CVC. The high-threshold group (platelet count ≤20×109/L had a significantly lower amount of platelet transfusions than the low-threshold group ≤10×109/L. The platelet transfusion amount was 1.44±0.77 vs. 2.05±1.13 (P=0.047), respectively. CONCLUSIONS: The chemotherapy regimens of DHAP, ICE, GDP, and Gemox can easily lead to thrombocytopenia. A high level of LDH in the peripheral blood and Ann Arbor stage III/IV are also associated with risk factors for thrombocytopenia. A 20×109/L prophylactic platelet transfusion threshold value is safer, more effective, and thus a better choice for DLBCL patients with CVC.

The effect of red blood cell transfusion on plasma hepcidin and growth differentiation factor 15 in gastric cancer patients: a prospective study.

BACKGROUND: Hepcidin and growth differentiation factor 15 (GDF-15) have been reported to be highly expressed in various cancers. Serum hepcidin and GDF-15 levels were demonstrated to be potential prognostic markers in cancers. This study aims to evaluate the effect of red blood cell (RBC) transfusion on plasma hepcidin and GDF-15 in gastric cancer patients. METHODS: In this prospective study, 40 patients with gastric cancer were eligible for this study. Peripheral blood samples were obtained before and within 24 h after RBC transfusion. A routine blood test was performed before transfusion and within 24 h post-transfusion. Plasma hepcidin, GDF-15, interleukin 6 (IL-6) and erythropoietin were determined by ELISA. RESULTS: In patients with metastasis, plasma hepcidin (P=0.02), and GDF-15 (P=0.01) levels were higher than without metastasis. Plasma hepcidin was increased after RBC transfusion (P=0.001), while plasma erythropoietin was decreased after transfusion (P=0.03). However, RBC transfusion did not affect plasma GDF-15 (P=0.32) and IL-6 (P=0.12). The effect of RBC transfusion on variables did not differ between metastatic and non-metastatic patients. The mean percentage change of hepcidin in transfusion volume 4 unit (U) was more than 2 U. CONCLUSIONS: RBC transfusion could increase plasma hepcidin and have no effect on plasma GDF-15 in gastric patients.

Perioperative blood transfusion has no effect on overall survival after esophageal resection for esophageal squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: The impact of perioperative blood transfusion (PBT) on the prognosis of esophageal cancer patients remains inconclusive. The purpose of this study was to assess the association between PBT and survival in esophageal squamous cell carcinoma (ESCC) patients. MATERIALS AND METHODS: In this retrospective study, patients with ESCC who underwent esophageal resection from January 2008 to December 2011 were analyzed. The overall survival and postoperative outcomes between PBT and non-PBT patients were compared using Cox regression and propensity score matching (PSM) analysis. RESULTS: A total of 935 patients were enrolled in this study. Before PSM, the 5-year overall survival rates in PBT and non-PBT patients were 48.4% and 56.3% (P = 0.001), respectively. The postoperative infection rate in PBT patients was 32.32%, which exceeded the rate of 24.22% in non-PBT patients (P = 0.008). PSM created 306 pairs of patients. After PSM, the 5-year overall survival rates in PBT and non-PBT patients were 49.4% and 51.0% (P = 0.334), respectively. The postoperative infection rate in PBT patients was 31.04%, which was higher than the rate of 26.47% in non-PBT patients (P = 0.105). Multivariable Cox regression analyses showed that PBT was not an independent risk factor for overall survival (HR: 0.792, 95% CI: 0.615-1.021, P = 0.072). CONCLUSION: Perioperative blood transfusion has no effect on the overall survival of ESCC patients.

Thrombelastography coagulation index may be a predictor of venous thromboembolism in gynecological oncology patients.

AIM: Venous thromboembolism (VTE) is a well-recognized complication in gynecological oncology patients, and has an impact on the overall outcome. The purpose of this study was to identify whether thrombelastography (TEG) predicts VTE in gynecological oncology patients. METHODS: This retrospective study included patients with gynecological oncology who were hospitalized at the Fujian Provincial Cancer Hospital from May 2014 to April 2016. Univariate and logistic regression multivariate analyses were performed to determine the clinical and laboratorial factors for VTE in gynecological oncology patients. The sensitivity and specificity of predictors was calculated using receiver operating characteristic curve. RESULTS: The study included 376 patients; 39 (10.37%) developed VTE. Logistic regression multivariate analysis revealed that TEG coagulation index (CI) value, D-dimer, arrhythmia, coronary heart disease, surgery within four weeks and chemotherapy within four weeks were independent risk factors for VTE. The area under the curve values were 0.71 (95% confidence interval 0.63-0.79, P = 0.000) for TEG CI and 0.67 (95% confidence interval 0.58-0.76, P = 0.000) for D-Dimer. The TEG CI cut-off value was 2.55, which had 53.8% sensitivity and 75.4% specificity for VTE. CONCLUSIONS: These results indicated that the TEG CI value may be predictive of VTE in gynecological oncology patients.

The impact of hemoglobin level and transfusion on the outcomes of chemotherapy in gastric cancer patients.

OBJECTIVE: To examine the impact of hemoglobin levels in predicting outcomes and evaluate whether transfusion could improve the outcomes of chemotherapy on gastric cancer patients. METHODS: A total 310 patients were divided into two groups: high Hb group (Hb >90 g/L) and low Hb group (Hb <90 g/L). A portion of patients in low Hb group received transfusion. The effect of hemoglobin level on the chemotherapy outcomes was determined according to the comparison between patients with high hemoglobin and patients with low hemoglobin without transfusion. The effect of transfusion on the chemotherapy outcomes was evaluated by comparing the two low groups (with and without transfusion). RESULTS: A total of 310 patients were within the study criteria. Among them, 27.7% patients in high Hb group, 44.5% patients in low Hb without transfusion and 27.7% patients in low Hb with transfusion were followed up. The 5-years survival rates of high Hb group, low Hb group without transfusion and with transfusion were respectively 29%, 10% and 8%. The survival rate of patients in Hb group without transfusion was higher. The chemotherapy rates of patients in high Hb group, low Hb without transfusion group and with transfusion group were respectively 32.56%, 42.03% and 18.6%. CONCLUSION: Low nadir Hb (<90 g/L) during chemotherapy had an effect on the survival and chemotherapy response rate. The chemotherapy outcomes could not be improved through increasing Hb level by red blood cell (RBC) transfusion.

Crystal structure confirmation of JHP933 as a nucleotidyltransferase superfamily protein from Helicobacter pylori strain J99.

Helicobacter pylori is a well-known pathogen involved in the development of peptic ulcer, gastric adenocarcinoma and other forms of gastric cancer. Recently, there has been more considerable interest in strain-specific genes located in plasticity regions with great genetic variability. However, little is known about many of these genes. Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. JHP933, a conserved putative protein of unknown function, is encoded by the gene in plasticity region of H. pylori strain J99. Here we have determined the structure of JHP933. Our work demonstrates that JHP933 is a nucleotidyltransferase superfamily protein with a characteristic αßαßαßα topology. A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933. Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.