[ ABSTRACT] AIM: To investigate the effects of bone marrow mesenchymal stem cells ( BMSCs) modified by programed death ligand-1 immunoglobulin ( PDL1 Ig) gene on immune rejection of orthotopic liver transplantation in rats. METHODS:Rat BMSCs were cultured and identified.The protein expression of PDL1 Ig in the BMSCs 72 h after infection with pAdEasy-1/PDL1 Ig was detected by Western blot.Mixed lymphocyte reaction was used to detect the inhibitory effect of BMSCs on the viability of T-lymphocytes in peripheral blood.The male Wistar rats were used as donors (n=40), and the male SD rats were used as recipients ( n=40 ) .The rat model of orthotopic liver transplantation was established by im-proved cuff method for observing acute rejection.The rats were randomly divided into control group, BMSCs treatment group, BMSCs/GFP treatment group and BMSCs/PDL1 Ig treatment group with 10 pairs each.Five rats were executed at the 7th day and the remains were used for measuring the survival time.RESULTS:The expression of PDL1 Ig in the BM-SCs was detected after pAdEasy-1/PDL1 Ig infection.The effect of BMSCs/PDL1 Ig on the viability of the lymphocytes was stronger than that of BMSCs/GFP.The level of IL-4 in BMSCs/PDL1 Ig group was significantly higher than that in the other 3 groups, while the levels of IFN-γand IL-2 were significantly decreased.The liver function in BMSCs/PDL1 Ig group was significantly improved and the levels of ALT, AST and TBil were almost recovered to normal at the 7th day after transplan-
tation.Severe rejection reaction was observed in control group, and rejection reactions were decreased with different degrees in BMSCs treatment group and BMSCs/GFP treatment group.Much slighter rejection reaction and significantly longer sur-vival time were showed in BMSCs/PDL1 Ig group than those in the other 3 groups.CONCLUSION:PDL1 Ig-modified BM-SCs inhibit the rejection of liver transplantation in rats and induce the immune tolerance, and the effect is better than that of BMSCs alone.

Objective:To investigate the nurses' attitude towards open visitation policy in intensive care unit (ICU) and its potential influence factors, and further to provide evidence for carrying out this policy in ICU.Methods:A self-designed, anonymous online questionnaire of "attitude of ICU nurses to open visiting system in ICU" was performed in 31 provinces, autonomous regions and municipalities in China from October to December 2019, using convenient sampling method approach. Only nurses working in ICU (including specialized ICU, but excluding the critical ward in general ward) and willing to participate in the survey were included. The survey included 35 items, including the general information of each participant, the attitude towards the implementation of the open visitation system in ICU and its potential influencing factors. Ordinal Logistic regression analysis was used to identify the significant influencing factors.Results:A total of 1 558 questionnaires were sent out and 1 546 effective questionnaires were retrieved, with a response rate of 99.2%. Overall, 32.2% of them agreed with the policy, 41.3% of them disagree with the policy and 26.5% of them were uncertain. The Ordinal Logistic regression analysis showed that the independent influencing factors of ICU nurses' attitude towards open visitation policy including the possibility of increasing healthcare-associated infection [disagree: β = 1.327, 95% confidence interval (95% CI) was 0.242 to 2.413, P = 0.017; uncertain: β = 0.697, 95% CI was 0.244 to 1.151, P = 0.003], the improvement of nurses' job satisfaction (disagree: β = -1.406, 95% CI was -1.750 to -1.062, P = 0.000; uncertain: β = -0.748, 95% CI was -1.030 to -0.466, P = 0.000), the information support for medical staffs from family members (disagree: β = -0.644, 95% CI was -1.048 to -0.240, P = 0.002; uncertain: β = -0.422, 95% CI was -0.721 to -0.124, P = 0.006), the feasibility that the family members can assist the nurses in the basic nursing for patients (uncertain: β = -0.465, 95% CI was -0.729 to -0.202, P = 0.001), reducing the time that a nurse spent on caring for the patients (uncertain: β = 0.349, 95% CI was 0.052 to 0.646, P = 0.021), improving early rehabilitation (disagree: β = -0.593, 95% CI was -1.166 to -0.019, P = 0.043), and getting psychological support for patients from family members (disagree: β = 1.293, 95% CI was 0.426 to 2.159, P = 0.003), family members' satisfaction (disagree: β = -0.981, 95% CI was -1.431 to -0.531, P = 0.000). Conclusion:ICU nurses in China have realized that open visitation policy has positive effect on patients' early rehabilitation, willing to live and satisfaction; meanwhile, this policy may need more improvement in many ways such as healthcare-associated infection control, disinfection and isolation, allocation of human resources and time spent treating and caring for patients.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.