Identification of cytokines in benign and malignant thymus tumors: based on Mendelian randomization and proteomics.

Objective: The aim of this study was to identify potential causal cytokines in thymic malignancies and benign tumors from the FinnGen database using Mendelian randomization (MR). Methods: In this study, data from genome-wide association studies (GWAS) of 91 cytokines were used as exposure factors, and those of thymic malignant tumors and thymic benign tumors were the outcome variables. Two methods were used to determine the causal relationship between exposure factors and outcome variables: inverse variance weighting (IVW) and MR-Egger regression. Sensitivity analysis was performed using three methods, namely, the heterogeneity test, the pleiotropy test, and the leave-one-out test. Results: There was a causal relationship between the expression of fibroblast growth factor 5, which is a risk factor for thymic malignant tumors, and thymic malignant tumors. C-C motif chemokine 19 expression, T-cell surface glycoprotein CD5 levels, and interleukin-12 subunit beta levels were causally related to thymic malignant tumors and were protective. Adenosine deaminase levels, interleukin-10 receptor subunit beta expression, tumor necrosis factor (TNF)-related apoptosis-inducing ligand levels, and TNF-related activation-induced cytokine levels showed a causal relationship with thymic benign tumors, which are its risk factors. Caspase 8 levels, C-C motif chemokine 28 levels, interleukin-12 subunit beta levels, latency-associated peptide transforming growth factor beta 1 levels, and programmed cell death 1 ligand 1 expression showed a causal relationship with thymic benign tumors, which are protective factors. Sensitivity analysis showed no heterogeneity. Conclusion: Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.

Roles of IL-4, IL-13, and Their Receptors in Lung Cancer.

Interleukin (IL)-4 and IL-13 are the main effectors of innate lymphoid cells (ILC2) of the type 2 innate immune response, which can carry out specific signal transmission between multiple cells in the tumor immune microenvironment. IL-4 and IL-13 mediate signal transduction and regulate cellular functions in a variety of solid tumors through their shared receptor chain, the transmembrane heterodimer interleukin-4 receptor alpha/interleukin-13 receptor alpha-1 (type II IL-4 receptor). IL-4, IL-13, and their receptors can induce the formation of a variety of malignant tumors and play an important role in their progression, growth, and tumor immunity. In order to explore possible targets for lung cancer prediction and treatment, this review summarizes the characteristics and signal transduction pathways of IL-4 and IL-13, and their respective receptors, and discusses in depth their possible role in the occurrence and development of lung cancer.

Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study.

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

Evidence based on Mendelian randomization: Causal relationship between mitochondrial biological function and lung cancer and its subtypes.

OBJECTIVE: This study aimed to investigate the causal relationship between mitochondrial biological function and lung cancer, including its subtypes, via MR. METHODS: SNPs significantly associated with lung cancer and its subtypes were employed as instrumental variables. MR-Egger regression, simple mode, weighted mode, simple median, and weighted median, were utilized to determine the causal relationship between the exposure factor and the occurrence of lung cancer and its subtypes. RESULTS: NADH dehydrogenase (ubiquinone) flavoprotein 2 and transmembrane protein 70 were found to have a causal relationship with lung adenocarcinoma, acting as protective factors. The causal relationship between mitochondrial import inner membrane translocase subunit and NADH dehydrogenase (ubiquinone) iron-sulfur protein 4 and small-cell lung cancer was established as a risk factor. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 exhibited a causal relationship with small-cell lung cancer, acting as a protective factor. Furthermore, NAD-dependent protein deacylase sirtuin-5 was causally linked to lung squamous cell carcinoma, serving as a protective factor. A funnel plot demonstrated the symmetrical distribution of the SNPs. Thew pleiotroy test (P > 0.05) and "leave-one-out" test validated the relative stability of the results. CONCLUSION: This study established a causal relationship between mitochondrial biological function and lung cancer, including its subtypes.

Research on the application and effect of flipped-classroom combined with TBL teaching model in WeChat-platform-based biochemical teaching under the trend of COVID-19.

BACKGROUND: Biochemistry is a core subject in clinical medical education. The traditional classroom teaching model led by teachers is often limited to the knowledge transfer of teachers and the passive acceptance of students. It lacks interactive and efficient teaching methods and is not enough to meet the learning needs and educational goals of modern students. The combination of WeChat public platform, flipped classroom and TBL teaching model is closer to the needs of real life and workplace, helping students to cultivate comprehensive literacy and the ability to solve practical problems. At the same time, this teaching model has yet to be used in biochemistry courses. OBJECTIVE: To explore the influence of the mixed teaching model of flipped classroom and combining TBL based on WeChat public platform upon undergraduates in biochemistry. METHODS: Using the mixed research method of quasi-experimental research design and descriptive qualitative research, 68 students were selected into the traditional and the blended teaching groups. Among them, the blended teaching group adopts the blended teaching model of flipped classroom combined with TBL based on the WeChat platform to learn biochemical courses. In this study, an independent sample t-test was intended to analyze the differences in final scores, a chi-square test was served to analyze the differences in satisfaction questionnaires, and thematic analysis was used to analyze semi-structured interview data. RESULTS: Compared with the traditional teaching model, the mixed teaching model significantly improved students' final exam scores (P < 0.05). The teaching satisfaction of the mixed teaching group was also higher than that of the traditional teaching group with statistical significance (P < 0.05). The results of the interviews with eight students were summarized into three topics: (1) Stimulating interest in learning; (2) Improving the ability of autonomous learning; (3) Recommendations for improvement. CONCLUSIONS: The combination of the WeChat platform and flipped classroom with TBL has a positive effect on improving medical students' autonomous learning ability and problem-solving ability. The research shows that the teaching mode of flipped classroom combined with TBL based on the WeChat platform is effective and feasible.

Application effect evaluation of hybrid biochemistry teaching model based on WeChat platform under the trend of COVID-19.

With WeChat platform as the carrier, we explored the effect of online and offline mixed teaching mode applied to Biochemistry teaching. One hundred and eighty-three students from the 4-year nursing major of Xinglin College of Nantong University in 2018 and 2019 were used as the observation group, using online and offline hybrid teaching methods, and 221 students majoring in 4-year nursing from Xinglin College of Nantong University in 2016 and 2017 were the control group, where the traditional classroom teaching method was adopted. The usual stage scores and final scores of the observation group were significantly higher than those of the control group (P < .01). The micro-lecture videos, animations, and periodic assessment methods of the WeChat platform under "Internet+" can greatly stimulate students' interest in learning, thereby significantly improving academic performance and autonomous learning ability.

Developing and validating a survival prediction model based on blood exosomal ceRNA network in patients with PAAD.

BACKGROUND: Among the most lethal cancers, pancreatic adenocarcinoma (PAAD) is an essential component of digestive system malignancies that still lacks effective diagnosis and treatment methods. As exosomes and competing endogenous RNA (ceRNA) regulatory networks in tumors go deeper, we expect to construct a ceRNA regulatory network derived from blood exosomes of PAAD patients by bioinformatics methods and develop a survival prediction model based on it. METHODS: Blood exosome sequencing data of PAAD patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, lncRNA, and circRNA were differentially analyzed by R. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Then, we conducted GO and KEGG enrichment analysis of mRNA in the ceRNA network. Genes that express differently in pancreatic cancer tissues compared with normal tissues and associate with survival (P < 0.05) were determined as Hub genes by GEPIA. We identified optimal prognosis-related differentially expressed mRNAs (DEmRNAs) and generated a risk score model by performing univariate and multivariate Cox regression analyses. RESULTS: 205 DEmRNAs, 118 differentially expressed lncRNAs (DElncRNAs), and 98 differentially expressed circRNAs (DEcircRNAs) were screened out. We constructed the ceRNA network, and a total of 26 mRNA nodes, 7 lncRNA nodes, 6 circRNA nodes, and 16 miRNA nodes were identified. KEGG enrichment analysis showed that the DEmRNAs in the regulatory network were mainly enriched in Human papillomavirus infection, PI3K-Akt signaling pathway, Osteoclast differentiation, and ECM-receptor interaction. Next, six hub genes (S100A14, KRT8, KRT19, MAL2, MYO5B, PSCA) were determined through GEPIA. They all showed significantly increased expression in cancer tissues compared with control groups, and their high expression pointed to adverse survival. Two optimal prognostic-related DEmRNAs, MYO5B (HR = 1.41, P < 0.05) and PSCA (HR = 1.10, P < 0.05) were included to construct the survival prediction model. CONCLUSION: In this study, we successfully constructed a ceRNA regulatory network in blood exosomes from PAAD patients and developed a two-gene survival prediction model that provided new targets which shall aid in diagnosing and treating PAAD.

Analysis of Competitive Endogenous RNA Regulatory Network of Exosomal Breast Cancer Based on exoRBase.

Objective: To construct a competitive endogenous RNA (ceRNA) regulatory network derived from exosomes of human breast cancer (BC) by using the exoRbase database, to explore the possible pathogenesis of BC, and to develop new targets for future diagnosis and treatment. Methods: The exosomal gene sequencing data of BC patients and normal controls were downloaded from the exoRbase database, and the expression profiles of exosomal mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) were analyzed by using R language. Use Targetscan and miRanda database to jointly predict and differentially express miRNA (microRNA), miRNA combined with mRNA. The miRcode database was used to predict the miRNA combined with differentially expressed lncRNA, and the starBase database was used to predict the miRNA combined with circRNA in the difference table. The related mRNA, circRNA, lncRNA, and their corresponding miRNA prediction data were imported into Cytoscape software to visualize the ceRNA network. Enrichment analysis and visualization of KEGG were carried out using KOBAS. Hub gene was determined by Cytohubba plug-in. Results: Forty-two differentially expressed mRNA, 43 differentially expressed circRNA, and 26 differentially expressed lncRNA were screened out. The ceRNA network was constructed by using Cytoscape software, including 19 mRNA nodes, 2 lncRNA nodes, 8 circRNA nodes, and 41 miRNA nodes. KEGG enrichment analysis showed that differentially expressed mRNA in the regulatory network mainly enriched the p53 signaling pathway. Find the key Hub gene PTEN. Conclusion: The ceRNA regulatory network in blood exosomes of BC patients has been successfully constructed in this study, which provides an exact target for the diagnosis and treatment of BC.

Effect of bilateral paravertebral nerve block on cognitive function in elderly patients undergoing radical gastrectomy for gastric cancer: a prospective randomized double-blind controlled trial.

OBJECTIVE: To investigate the effect of a bilateral paravertebral block (PVB) on cognitive function in elderly patients undergoing radical gastrectomy for gastric cancer. METHODS: Sixty patients (40 men and 20 women) aged 65-80 undergoing radical gastrectomy surgery under general anaesthesia were included and randomly assigned to either the PVB group or the control group. Patients in the PVB group had before incision a single-shot ultrasound-guided bilateral PVB at the T8 level with 20 mL of ropivacaine 0.375%, while patients in the control group had no block. Patients in both groups had a BIS-guided total intravenous anaesthesia with propofol and remifentanil infusions. Postoperative cognitive function assessed by the mini-mental state examination (MMSE) and NSE (neuron-specific enolase) was the primary outcome. RESULTS: The awareness time in group PVB was shorter than that in the group C, and the propofol and remifentanil dosages were less than that in group C (P<0.001, P = 0.007, respectively). Furthermore, the change of the MMSE score and the NSE concentration was significant from day0 to day1 and day1 to day2. (P<0.001). CONCLUSION: A single-shot bilateral PVB active throughout radical gastrectomy for gastric cancer reduces the needs for general anaesthetic agents and improve postoperative recovery, along with a surrogate evidence for neuroprotective effects. TRIAL REGISTRATION: ChiCTR2200060088 . Registered 18 May 2022.

Diagnostic value of exosome derived long noncoding RNA in gastric cancer in Chinese population: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Objective to systematically evaluate the diagnostic value of long noncoding RNA (lncRNA) in gastric cancer (GC) in the Chinese population. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang Database were searched. According to the search strategy and inclusion and exclusion criteria, 2 staff members screened the relevant kinds of literature from January 2010 to December 2020 and extracted the relevant data. Revman5.3, Meta-Disc1.4, and Stata15.1 software were used to analyze the relationship between lncRNA from exosomes and the diagnosis of GC. The combined values of sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic curve was drawn and the area under the ROC curve (AUC) value was calculated. RESULTS: In 9 studies, 1314 samples were included, including 792 cases in the case group and 522 cases in the control group. The combined SEN was 0.82 (95% CI: 0.77-0.86), the combined SPE was 0.78 (95% CI: 0.72-0.83), the combined positive likelihood ratio was 3.7 (95% CI: 2.9-4.6), the negative likelihood ratio was 0.23 (95% CI: 0.18-0.29), and the DOR was 16 (95% CI: 12-23), AUC was 0.87 (95% CI: 0.84-0.90). Subgroup analysis showed that the SEN, SPE, likelihood ratio, DOR, and AUC of plasma-derived lncRNA in the diagnosis of GC were better than those of serum. CONCLUSIONS: Exosome-derived lncRNA may be a new potential biomarker for the clinical diagnosis of GC.