Real-time monitoring of glucose metabolism and effects of metformin on HepG2 cells using 13C in-cell NMR spectroscopy.

Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13C in-cell NMR spectroscopy. Metabolic tracing with U-13C6-glucose revealed that metformin significantly increased the production of 13C-G3P and 13C-glycerol, which were reported to attenuate liver cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13C-lactate, 13C-alanine, 13C-glycine, and 13C-glutamate. Moreover, the expression levels of enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine.

Significance of serum sestrin2 as a biomarker of severity and functional outcome in acute intracerebral hemorrhage: a prospective observational longitudinal study.

BACKGROUND: Sestrin2 is a highly conserved stress-inducible protein with neuroprotective properties. Herein, we investigated the prognostic significance of serum sestrin2 in human intracerebral hemorrhage (ICH). METHODS: In this prospective observational longitudinal study, we enrolled 126 patients with supratentorial ICH as cases together with 126 healthy individuals as controls. Severity indicators were National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Prognostic parameters were early neurologic deterioration (END) and post-stroke 6-month poor prognosis [modified Rankin Scale (mRS) scores of 3-6]. Multivariate analysis was performed to assess relations of serum sestrin2 levels to severity and prognosis. RESULTS: Patients had statistically significantly higher serum sestrin2 levels than controls. Serum sestrin2 levels of patients were independently correlated with NIHSS scores and hematoma volume, as well as were substantially elevated in order of mRS scores from 0 to 6. Serum sestrin2 was identified as an independent predictor of END and poor prognosis. Based on the receiver operating characteristic curve, serum sestrin2 had a similar predictive ability for END and poor prognosis, as compared to NIHSS scores and hematoma volume. Prediction models of END and poor prognosis, in which serum sestrin2, NIHSS scores and hematoma volume were integrated, were visually described via nomogram, were reliable and stable under calibration curve and were of clinical benefit using decision curve analysis. Also, prediction model of poor prognosis showed dramatically higher discriminatory efficiency than any of NIHSS scores, hematoma volume and serum sestrin2. CONCLUSION: Serum sestrin2 levels, which are obviously increased following acute ICH, are independently related to illness severity and poor clinical outcomes, substantializing serum sestrin2 as a clinically valuable prognostic biomarker of ICH.

Application of enhanced recovery after surgery following liver transplantation.

OBJECTIVE: To investigate the effect of an enhanced recovery after surgery (ERAS) programme following liver transplantation and to further clarify the safety and clinical application value of an ERAS programme. METHODS: A retrospective analysis of 250 patients who underwent liver transplant at Beijing You'an Hospital affiliated to Capital Medical University between March 2019 and December 2021 was conducted. According to different perioperative management methods, patients were divided into a control group (120 cases) and an ERAS group (130 cases). Postoperative safety indicators, efficacy indicators and economic indicators were compared between the two groups. RESULTS: There was no significant difference in the safety indicators between the two groups. The ERAS group showed significantly lower results compared with the control group in terms of ventilator-associated pneumonia, urinary tract infection, pressure injury of oral and nasal mucosa, postoperative pain score 5 days after surgery and the incidence of delirium, whereas the Barthel score 10 days after surgery was significantly higher. There was no significant difference between the two groups in skin pressure injury or the Subjective Global Assessment grade 10 days after surgery. The length of intensive care unit stay, the total length of stay after surgery and the 10-day medical expenses after surgery were significantly lower in the ERAS group than in the control group. CONCLUSION: The application of an ERAS programme after liver transplantation can effectively promote the postoperative recovery of patients and reduce medical costs. Studies have shown that the ERAS programme has important application value in improving the postoperative quality of life and reducing the economic burden of patients after liver transplantation. This programme provides a new concept for related clinical improvement and application.

Random-forest algorithm based biomarkers in predicting prognosis in the patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) one of the most common digestive system tumors, threatens the tens of thousands of people with high morbidity and mortality world widely. The purpose of our study was to investigate the related genes of HCC and discover their potential abilities to predict the prognosis of the patients. METHODS: We obtained RNA sequencing data of HCC from The Cancer Genome Atlas (TCGA) database and performed analysis on protein coding genes. Differentially expressed genes (DEGs) were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted to discover biological functions of DEGs. Protein and protein interaction (PPI) was performed to investigate hub genes. In addition, a method of supervised machine learning, recursive feature elimination (RFE) based on random forest (RF) classifier, was used to screen for significant biomarkers. And the basic experiment was conducted by lab, we constructe a clinical patients' database, and obtained the data and results of immunohistochemistry. RESULTS: We identified five biomarkers with significantly high expression to predict survival risk of the HCC patients. These prognostic biomarkers included SPC25, NUF2, MCM2, BLM and AURKA. We also defined a risk score model with these biomarkers to identify the patients who is in high risk. In our single-center experiment, 95 pairs of clinical samples were used to explore the expression levels of NUF2 and BLM in HCC. Immunohistochemical staining results showed that NUF2 and BLM were significantly up-regulated in immunohistochemical staining. High expression levels of NUF2 and BLM indicated poor prognosis. CONCLUSION: Our investigation provided novel prognostic biomarkers and model in HCC and aimed to improve the understanding of HCC. In the results obtained, we also conducted a part of experiments to verify the theory described earlier, The experimental results did verify our theory.

Social supports and mental health: a cross-sectional study on the correlation of self-consistency and congruence in China.

BACKGROUND: Psychosocial job characteristics require nursing staff with high self-consistency and good mental health. However, the attention and effort of such study remained very limited in China. METHODS: A self-administered questionnaire was distributed to the bedside nurses in an affiliated hospital of Hebei Medical University, China. Of 218 registered bedside nurses eligible to participate in the survey anonymously, the data producing sample of 172 subjects resulted in a 79 % of effective response rate.. The Social Support Rating Scale was used to measure social support, and the Self-Consistency and Congruence Scale were used to measure mental health. RESULTS: Compared with the normal referenced group of college students, higher self-flexibility scores, lower self-conflict and self-stethoscope scores from the sample group were obtained with statistical significance in self-conflict scores. The close correlations were observed between participants' social support and Self-Consistency and Congruence Scale score. The difference of Social Support Rating Scale score was significant in demographic features including years of work, marital status, only child family, and levels of cooperation with other health worker. CONCLUSIONS: Bedside nurses in this study show a better inner harmony, and their Self-Consistency and Congruence closely correlates with the levels of social support. Thus, it is substantial to improve inner perception of support and external factors, such as the workplace support, and offer beneficial social environment to improve the bedside nurse's sub-health symptoms and decrease the high turnover rate.

Organoids: Construction and Application in Gastric Cancer.

Gastric organoids are biological models constructed in vitro using stem cell culture and 3D cell culture techniques, which are the latest research hotspots. The proliferation of stem cells in vitro is the key to gastric organoid models, making the cell subsets within the models more similar to in vivo tissues. Meanwhile, the 3D culture technology also provides a more suitable microenvironment for the cells. Therefore, the gastric organoid models can largely restore the growth condition of cells in terms of morphology and function in vivo. As the most classic organoid models, patient-derived organoids use the patient's own tissues for in vitro culture. This kind of model is responsive to the 'disease information' of a specific patient and has great effect on evaluating the strategies of individualized treatment. Herein, we review the current literature on the establishment of organoid cultures, and also explore organoid translational applications.

Clinically ill patients' experiences of early mobilisation after liver transplantation: a qualitative study using Pender's health promotion model.

The aim of this study is to explore the factors influencing early mobilisation behaviours and patients' needs in critically ill patients after liver transplantation (LT). This interview study used phenomenological research, and Pender's health promotion model (HPM) was used to construct the interview guide. With the use of purposeful sampling, a total of 19 critically ill patients who experienced early mobilisation after LT were recruited at three tertiary hospitals in Beijing from August to November 2022. Data were collected through semi-structured interviews and analysed using Colaizzi's seven-step method. Nine themes were categorised into the three domains of Pender's HPM. The first domain was individual characteristics and experiences: (1) symptoms of end-stage liver disease limiting premobility behaviours and (2) previous treatment experience affecting understanding of early mobilisation after LT. The second domain was behaviour-specific cognition and affect: (3) coexistence of benefits and concerns in early mobilisation after LT, (4) barriers to early mobilisation after LT, (5) high self-efficacy in early mobilisation after LT, (6) individual differences in early mobilisation and (7) support and encouragement from family, wardmates and medical staff. The final domain was behavioural outcomes: (8) the need for sufficient staff, a quiet environment, safety, goals, guidance and family participation and (9) a strong willingness to comply with early mobilisation plans. The three areas and nine themes extracted in this study are helpful for the long-term development of early mobilisation in patients after LT.

STAT1 suppresses the transcriptional activity of TRIM21 in gastric cancer.

PURPOSE: Tripartite motif-containing protein 21 (TRIM21) has E3 ubiquitin ligase activity and is involved in the regulation of various biological processes in vivo. TRIM21 has been found to have strong associations with various cancers. However, its role in gastric cancer is unclear. METHODS: The TCGA database was screened to obtain TRIM21 using WGCNA and PPI analyses. The TCGA database was used to evaluate the correlation of TRIM21 expression with patients' clinical characteristics, prognosis, functional enrichment and immune cell infiltration. The role of TRIM21 in cell proliferation, apoptosis and invasion was verified by in vivo and in vitro assays. The UCSC and JASPAR databases were used to evaluate the regulatory role of STAT1 on TRIM21 transcription. Finally, dual-luciferase reporter assay was used to confirm the regulation of TRIM21 transcriptional activity by STAT1. RESULTS: As a key gene, high expression of TRIM21 inhibited the gastric cancer growth and was significantly enriched in apoptosis, cell proliferation, and JAK/STAT signaling pathways. TRIM21 expression was positively correlated with a variety of TICs, including T cells, NK cells, and DCs. In vivo assays, TRIM21 inhibited functions in gastric cancer cell lines, including inhibition of proliferation and migration, and promotion of apoptosis. Database analysis and dual-luciferase reporter assay showed that STAT1 inhibited the transcriptional activity of TRIM21. In vivo assays confirmed that TRIM21 inhibited tumor growth, and STAT1 expression was negatively correlated with STAT1. CONCLUSION: TRIM21 is a tumor-suppressive gene in gastric cancer, and its transcriptional activity is inhibited by STAT1.

Role of CD155/TIGIT in Digestive Cancers: Promising Cancer Target for Immunotherapy.

The tumor microenvironment restricts the function and survival of various immune cells by up-regulating inhibitory immune checkpoints, and participates in the immune escape of tumors. The development of immunotherapies targeting immune checkpoints, such as programmed cell death receptor 1 antibody and anti-cytotoxic T lymphocyte-associated antigen 4 antibody, has provided many options for cancer treatment. The efficacy of other immune checkpoint inhibitors is also under development and research. Among them, T cell immunoreceptor with Ig and ITIM domains (TIGIT) has shown excellent clinical application prospects. Correspondingly, poliovirus receptor (PVR, CD155), one of the main ligands of TIGIT, is mainly expressed in various human malignant tumors and myeloid cells. CD155 interacts with TIGIT on natural killer cells and T cells, mediating inhibitory immunomodulatory regulation. This study summarized the mechanism of CD155/TIGIT in regulating immune cells and its role in the occurrence and development of digestive system tumors, aiming to provide a new perspective for immunotherapy of digestive cancers.

MCEMP1 is a potential therapeutic biomarker associated with immune infiltration in advanced gastric cancer microenvironment.

BACKGROUND: Over the last decade, breakthroughs have been made in cancer immunotherapy. However, for advanced gastric cancer (AGC), the complexity and heterogeneity of the tumor microenvironment (TME) has been the biggest challenge for immunotherapy. Therefore, an intensive study on TME of AGC is necessary. METHODS: ESTIMATE and CIBERSORT algorithms were applied to analyze the transcriptome data of AGC using TCGA database systematically. We identified mast cell-expressed membrane protein 1 (MCEMP1) as a potential prognostic marker by protein-protein interaction (PPI) and Univariate Cox regression. The expression of MCEMP1 was evaluated by immunohistochemistry (IHC) and quantitative real time PCR. We assessed prognostic values of MCEMP1 with use of Kaplan-Meier and Multivariate Cox regression analysis. Gene set enrichment analysis (GSEA) was used to analyze the molecular mechanism of MCEMP1. The correlation between MCEMP1 expression and tumor immune infiltration was analyzed by the TIMER database and CIBERSORT algorithm, which was confirmed by IHC. RESULTS: The mRNA and protein expression of MCEMP1 was up-regulated substantially and related to poor survival in AGC. GSEA analysis revealed that MCEMP1 was involved in the immune-related signaling pathways. We further demonstrated that the expression of MCEMP1 was correlated with multiple immune cells and immune checkpoints. The results of IHC indicated that there was a positive correlation between PD-L1 expression and MCEMP1, suggesting that MCEMP1 may affect the prognosis of AGC patients by regulating immune infiltration and the function of immune cells. CONCLUSION: MCEMP1 may serve as a biomarker associated with immune infiltration in TME and could be a potential therapeutic target for AGC patients.

Mediating effect of kinesiophobia between self-efficacy and physical activity levels in post-CABG patients: protocol for a prospective, multicentre, cross-sectional study in China.

INTRODUCTION: Physical activity (PA) can improve cardiac function, exercise capacity, and quality of life, in addition to reducing mortality by 20%-30% and preventing the recurrence of adverse cardiovascular events in patients following coronary artery bypass graft (CABG). However, PA levels are low in patients after CABG. This study intends to explore the mediating effect of kinesiophobia between self-efficacy and PA levels in patients following CABG. METHODS AND ANALYSIS: The proposed study constitutes a prospective, multicentre and cross-sectional study comprising 413 patients. Four teaching hospitals with good reputations in CABG will be included in the study. All of them are located in Beijing, China, and provide medical service to the whole country. This study will assess the following patient-reported outcome measures: demographic information, International Physical Activity Questionnaire-Long, Social Support Rating Scale, Cardiac Exercise Self-Efficacy Instrument, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale, and Tampa Scale for Kinesiophobia Heart. ETHICS AND DISSEMINATION: This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of The Sixth Medical Centre of PLA General Hospital (approval number: HZKY-PJ-2022-2). All study participants will provide written informed consent. Findings from this study will be published in Chinese or English for widespread dissemination of the results. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register, ChiCTR2100054098.

Sleep quality status, anxiety, and depression status of nurses in infectious disease department.

Objective: To investigate the current status of sleep quality and influencing factors of clinical nurses in infectious disease hospitals, and to provide basis and reference for improving their sleep status and providing psychological support. Methods: Using convenience sampling method, clinical nurses from a tertiary hospital for infectious diseases were selected as the survey subjects in September 2021. General information questionnaire, Pittsburgh Sleep Quality Questionnaire (PSQI), Generalized Anxiety Disorder Scale (GAD-7), Depression Screening Scale (PHQ-9) were used for questionnaire surveys, and multiple linear regression was used to analyze the impact of decreased sleep quality in clinical nurses factor. Results: A total of 460 questionnaires were returned, of which 442 were valid, effective rate is 96.09%. The Pittsburgh sleep quality index (PSQI) score of 442 clinical nurses was 7.07 ± 2.14, of which 60 (13.57%) had sleep disorders; the Generalized Anxiety Disorder Scale (GAD-7) score was 4.77 ± 3.50, of which 182 (41.18%) had varying degrees of anxiety; The score of PHQ-9 was 5.95 ± 3.79, of which 187 (42.31%) had different degrees of depressive symptoms. The stepwise multiple linear regression analysis which involved PHQ-9 and GAD-7 scores showed that: both the PHQ-9 score and the GAD-7 score were positively correlated with the sleep quality score, and the PHQ-9 score increased every time 1 point, sleep quality score increased by 0.239 points; GAD-7 score increased by 1 point, sleep quality score increased by 0.150 points. The overall model test (F = 109.760, P < 0.001) regression model is meaningful. Conclusion: Decreased sleep quality is common among clinical nurses in infectious disease hospitals, and the sleep status of nurses is positively correlated with anxiety and depression. Nursing managers pay attention to sleep quality of clinical nurses in infectious disease hospitals and carry out effective interventions to improve the sleep quality of nurses.

Overcome tumor relapse in CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans.

Effects of different brisk walking intensities on adherence and cardiorespiratory endurance of cardiac rehabilitation among patients with CHD after PCI: protocol for a randomised controlled trial.

INTRODUCTION: Cardiac rehabilitation (CR) is a critical treatment for patients with coronary heart disease after percutaneous coronary intervention. Unfortunately, participation and adherence of CR are unexpectedly poor. This study aims to test whether low-intensity or medium-intensity brisk walking is more helpful in improving early attendance, adherence and physical results. METHODS AND ANALYSIS: This randomised controlled study will compare the effects of low-intensity and medium-intensity brisk walking to improve adherence and cardiopulmonary endurance. Participants will be randomly allocated to low-intensity or medium-intensity groups and will be followed-up for 8 weeks. Primary and secondary outcome data will be collected at baseline and at 2, 4 and 8 weeks. Primary outcomes measure changes in oxygen consumption (VO2) peak value (mL/kg/min), as well as adherence. Secondary outcomes include changes in body mass index, oxygen pulse, maximal metabolic equivalent, breathing reserve, vital capacity, ratio of forced expiratory volume in 1 s to forced vital capacity, Δoxygen consumption/Δwork rate (ΔVO2/ΔWR), minute ventilation/carbon dioxide production and self-efficacy. ETHICS AND DISSEMINATION: Ethical approval and informed consent form have been obtained from the Ethics Committee of Hebei General Hospital (approval number: NA-2021-03). The study background and main objective, as well as potential benefits and risks, will be fully explained to the participants and their families. Findings from this study will be published on academic journals in Chinese or in English for widespread dissemination of the results TRIAL REGISTRATION NUMBER: ChiCTR2100047568.

The Role of the Respiratory Therapy Team in the Treatment of Patients With Acquired Immunodeficiency Syndrome Complicated With Pneumocystis Pneumonia Undergoing Mechanical Ventilation.

Objective: To explore the role of the respiratory therapy team in the treatment of patients with acquired immunodeficiency syndrome (AIDS) complicated with pneumocystis pneumonia (PCP) undergoing mechanical ventilation. Methods: A retrospective cross-sectional study was conducted, including 60 patients with AIDS complicated with PCP undergoing mechanical ventilation in our hospital from June 2019 to July 2020. In the process of patient respiratory monitoring, hospital transport, ventilator withdrawal, airway management, various aerosol treatments and controlled oxygen therapy, patients were divided into the control group and the case group according to whether the respiratory therapy team was involved or not (30 in the control group, 25 males and five females; 30 in the case group, 24 males and six females). The baseline data, mechanical ventilation time, hospitalization time and hospitalization expenses of the two groups were compared. Results: There was no statistically significant difference in baseline data between the case and control groups (P > 0.05). Compared with the control group, the case group had significantly shorter mechanical ventilation times and average hospitalization lengths and the average expenses decreased, and the difference was statistically significant (P < 0.05). Conclusion: The participation of the respiratory therapy team in the mechanical ventilation treatment of patients with AIDS and PCP helps to shorten the mechanical ventilation time and the average length of hospitalization and reduce the hospitalization expenses of patients. It is expected to increase the cure rate of such patients and improve their prognosis.

Metastasis Pattern and Survival Analysis in Primary Small Bowel Adenocarcinoma: A SEER-Based Study.

Background: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal tumor with high malignancy. The aim of this study was to comprehensively evaluate the distant metastasis pattern and establish nomograms predicting survival for SBA. Methods: From 2010 to 2015, patients diagnosed with SBA were identified based on the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was applied to compare survival differences between metastasis patterns. Then, univariate and multivariate cox analyses were applied to screened out independent prognostic factors of cancer-specific survival (CSS) and overall survival (OS), and identify the risk factors for metastasis of SBA. To assess the discrimination and calibration of nomograms, the concordance index (C-index), calibration curves, receiver-operating characteristic curve (ROC), and decision curve analysis (DCA) were calculated. Results: Kaplan-Meier curves revealed that metastasis patterns were significantly correlated with CSS (p < 0.001) and OS (p < 0.001). Then, the metastasis pattern was showed to be an independent prognostic factor of OS and CSS in patients with SBA, as well as age, grade, T stage, N stage, surgery, retrieval of regional lymph nodes, and chemotherapy. Combining these factors, we constructed prognostic nomograms, which suggested that the metastasis pattern made the greatest contribution to the survival of patients with SBA. Nomograms for OS and CSS had a C-index of 0.787 and 0.793, respectively. Calibration curves showed an excellent agreement between probability and actual observation in the training and validation cohort. Decision curve analysis also exhibited its clinical value with an improved net benefit. In addition, the models we constructed had better prognostic accuracy and clinical utility than traditional TNM staging based on C-index and ROC. Further, Cox regression analysis showed that old age, poor differentiation, N2, and not receiving chemotherapy were the risk factors for prognosis in patients with metastatic SBA. Conclusion: As an independent prognostic factor, the metastasis pattern exhibited the greatest predictive effect on OS and CSS for patients with SBA. Adjuvant chemotherapy had a positive effect on the survival of patients with SBA. Nomograms for predicting 3-and 5-year OS and CSS of patients with SBA were constructed, which could identify patients with higher risk and might be superior in predicting the survival of patients with SBA than TNM staging.

How does group cooperation help improve self-directed learning ability in nursing students? A trial of one semester intervention.

BACKGROUND: Self-directed learning (SDL) ability prepares nursing students to adapt to learning after graduation. Jiang An-li's four-dimension model of SDL ability includes the "ability of self-management, ability to apply learning strategy, ability to obtain information and ability to cooperate". Students learning in small heterogeneous groups get the opportunity to work with peers from different backgrounds. OBJECTIVE: To explore the effect of group cooperative learning on improving SDL ability and its possible path. DESIGN: A quasi-experimental design was adopted. PARTICIPANTS: Ninety nine sophomore nursing students (Mean age 21.29 ± 0.57) were enrolled in the study. Using the cluster sampling method, thirty students in one administrative class were arranged as a Group Cooperative Class (GCC) and another class (with 69 students) were arranged as a Conventional Class (CC). METHODS: The teaching materials in both the GCC and the CC were from the same course - Fundamental Nursing Theories. The teaching activities in the GCC focused on group learning while those in the CC focused on the educator. Scale of SDL Ability (SSDLA) was employed to measure the SDL ability. SSDLA data and class evaluations were collected. RESULTS: There were statistically significant differences in the total scores of SSDLA and sub dimensions of "ability of self-management", "ability to cooperate" between the GCC and the CC. The GCC scores of a paper test at the end of the semester were higher than those in the CC, with no statistical significance (p > 0.05). GCC students' evaluation of the course was higher than the CC's evaluation, but there was no statistical significance except on the questions of "diversity of teaching methods" and "flexibility of teacher-student interaction" (P < 0.05). CONCLUSIONS: The result of the current study is consistent with Jiang's four-dimension model and suggests that heterogeneous group learning in a small capacity class improves nursing students' SDL ability, possibly through improving their self-management and cooperation abilities.

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro, we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In vivo, we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3+CD8+ T cells and CD62L+CCR7+ central memory T cells (TCM) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.

Effect of peer support on patient anxiety during the coronary angiography or percutaneous coronary intervention perioperative period: a protocol for a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: The purpose of this study is to investigate the effect of peer support on patient anxiety during the perioperative period of coronary angiography or percutaneous coronary intervention (PCI). METHODS AND ANALYSIS: We will search the following databases (PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform, Google Scholar, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, Chinese BioMedical Database and Wanfang Data) from the date of database inception to January 2019. Only randomised controlled trials will be included. For the data analysis, we will use RevMan V.5.3.5 software to evaluate the risk of bias, and the heterogeneity will be investigated using the Q statistic and P index. Additionally, the Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the quality of evidence. ETHICS AND DISSEMINATION: No ethics approval will be required since this is a systematic review of published studies. We aim to report information regarding the effects of peer support on patient anxiety during the perioperative period of coronary angiography or PCI. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42019123290.

Efficacy and safety of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction cancer: a systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICI) have shown promising prospects in gastroesophageal junction (G/GEJ) cancer immunotherapy, many clinical trials have been carried out. Objective: To evaluate the efficacy and safety of ICI in G/GEJ cancer. Methods: The published English articles of PubMed, Cochrane Library, Embase, Web of Science were searched up to 30/09/2018. The efficacy and safety of ICI were analyzed by meta-analysis. Results: A total of 2003 patients from nine clinical trials were included. Anti-PD-1 treatment improved the 12-month, 18-month overall survival (OS) rate (RR, 1.79 p = 0.013; 2.20 p = 0.011) and prolonged the duration of response (DOR) (MSR, 3.27 p < 0.001). The objective response rate (ORR) in PD-L1+ patients was greater than PD-L1- (RR, 4.31 p < 0.001). Microsatellite instability-high (MSI-H) patients had higher ORR and disease control rate (DCR) than microsatellite stability (MSS) (RR, 3.40 p< 0.001; 2.26 p= 0.001). The most common grade ≥3 treatment-related adverse events (TRAEs) were fatigue, aspartate aminotransferase increased, hepatitis, pneumonitis, colitis, hypopituitarism. The TRAE incidence of anti-PD-1/PD-L1 was less than chemotherapy (TRAE RR = 0.64 p< 0.001; ≥3 TRAE RR = 0.37 p < 0.001). The incidence of ≥3 TRAEs of anti-PD-1/PD-L1 treatment was less than that of anti-CTLA-4 (11.7% vs 43.9%). Conclusions: ICI treatment could improve some but not all survival endpoints to advanced or metastatic G/GEJ cancer patients suggesting modest benefit and less adverse reactions. Anti-PD-1/PD-L1 therapy was more effective to PD-L1+, MSI-H, EBV+, or high tumor mutational burden patients.