Objective:To establish a nicotine-treatment and-withdrawal rat model and to evaluate its characteristics and application through analyzing 3 parameters.Methods:Male Sprague-Dawley rats,aged 10-11 weeks old,were randomly divided into normal saline group(subcutaneous injection of saline [0.5 ml/kg] for 6 weeks),nicotine-treated group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 6 weeks),and nicotine-withdrawn group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 3 weeks and followed by saline injection for additional 3 weeks).Body weight,food intake,and water intake of animals were recorded during the treatment in 3 groups.The model was evaluated through analyzing body weight,serum parameters and adipose tissue weights.Results:The body weight of rats,as well as the serum levels of triglyceride and insulin,were all decreased after nicotine treatment;the weights of subcutaneous fat,visceral fat and periaortic fat were also decreased.The above indicators increased after withdrawal of nicotine.Conclusion:The established model can be used to study multiple pharmacological effects of nicotine;it can also be used for smoking and smoking cessation related studies.

Objective:It has been proposed that blood pressure variability(BPV) is positively related to end-organ damage(EOD) in hypertension.The present work was designed to observe the effects of long-term treatment with nitrendipine and hydralazine on BPV and EOD in spontaneously hypertensive rats(SHR),to examine the hypothesis that lowering BPV with an antihypertensive drug is an important factor in organ protection.Design and methods:Drugs were mixed in rat chow.After 4 months of drug administration,blood pressure was recorded continuously in conscious freely moving rats for 24 h.The heart,kidneys,and brain were then isolated and examined.Results:It was found that nitrendipine significantly decreased blood pressure and BPV,and significantly decreased EOD score in SHR.Hydralazine decreased blood pressure,but did not lower BPV.No effect on EOD was found in hydralazine-treated rats.In control rat(n=38),EOD score was weakly related to systolic blood pressure(r=0.331,P<0.05) and closely related to long-term systolic BPV(r=0.551,P<0.01).In nitrendipine-treated rats,EOD score was closely related to long-term systolic BPV(r=0.602,P<0.01),but not to blood pressure level(r=0.174,P>0.05).Conclusion:BPV plays an important role in the organ-protecting effects of nitrendipine.

Objective:To compare the efficacy between chemotherapy with granulocyte colony-stimulating factor (G-CSF) and chemo-therapy with G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood hemato-poietic stem cells and hematological recovery post-transplantation in patients with malignant lymphoma. Methods:Autologous pe-ripheral blood hematopoietic stem cell mobilization data of 61 malignant lymphoma patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to October 2016 were included in this study. The mobilization effi-cacy and hematopoietic recovery were analyzed. Results:During mobilization, White blood cells (WBC) of all patients decreased to 1.0×109/L and platelets (PLT) dropped to 40×109/L. The successful mobilization rates of CD34+cell are 52.5%in chemotherapy plus G-CSF group and 90.5%in chemotherapy plus G-CSF+GM-CSF group (P=0.003). All patients successfully underwent hematopoietic recon-struction without transplantation-related mortality. Conclusion: Although chemotherapy with G-CSF+GM-CSF can significantly in-crease the effect of autologous peripheral blood hematopoietic stem cell mobilization, the reconstruction of hematopoietic function after transplantation and side reaction between the two groups are the same. Thus, chemotherapy with G-CSF+GM-CSF is not superior to chemotherapy with G-CSF in mobilizing autologous peripheral blood hematopoietic stem cells.

Objective: To evaluate the influence of happiness therapy intervention on the medication compliance and quality of life of acquired immune deficiency syndrome (AIDS) patients after discharge. Methods: A total of 106 adult AIDS patients discharged from hospital from July 2016 to July 2017 were randomly divided into control group (52 cases), observation group (54 cases). The control group was given routine health education and instruction, and three times of happiness therapy intervention were performed during the hospitalization. The observation group increased the number of happiness therapy intervention after discharge according to the patient′s medication compliance. The medication compliance scale and quality of life scale were used to evaluate the compliance rate and quality of life of patients in 2 groups at discharge, 3 months after discharge, 6 months after discharge, and 12 months after discharge. Results: There was no significant difference in medication compliance and quality of life at discharge and 3 months after discharge between the two groups (P>0.05). At 6 months and 12 months after discharge, the compliance rate and quality of life scores in the observation group was 90.74%(49/54), 88.89%(46/54) and (69.62 ± 5.82) points, (68.76 ± 5.63) points, respectively, 61.54% (32/52), 59.62% (31/52) and (52.12 ± 4.30) points, (52.05 ± 4.25) points in the control group, the difference was statistically significant (χ²=9.684, 9.035, t=8.638, 8.963, P<0.01). Conclusions The happiness therapy intervention during hospitalization can effectively improve the medication compliance and quality of life of AIDS patients. After the discharge, the happiness therapy intervention can provide the patients with long-term nursing programs, which can improve the adherence and quality of life of AIDS patients compared with the control group Have a better long-term effect.

Objective The purpose of this study was to investigate the differential expression of circRNAs in human blood, as a diagnostic marker for pre-diabetes and type 2 diabetes mellitus( T2DM). Methods Microarray analysis was used to select several differentially expressed circRNAs from three normal patients and three T2DM patients. Enlarge the sample size(normal controls,n=20;subjects with impaired glucose regulation,n=20;and type 2 diabetes mellitus,n=20) to determine a circRNA which the most evident differentially expressed by fluorescence quantitative PCR( Q-PCR). Then they were verified with expanded samples ( normal controls, n= 50; impaired glucose regulations,n=50;type 2 diabetes mellitus, n=50) by Q-PCR. Results A total of 2 953 differentially expressed circRNAs were found in microarray analysis, of which 1 439 were up-regulated and 1 514 were down-regulated. Nine differentially expressed circRNAs were selected from the 1 439 circRNAs that were up-regulated(hsa-circ-103838, hsa-circ-103965, hsa-circ-104227, hsa-circ-002117, hsa-circ-000094, hsa-circ-101226, hsa-circ-101720, hsa-circ-400029, and hsa-circ-100633). The Q-PCR results of the expanded sample( n=60) showed that the difference expression of hsa-circ-000094(Alias:has-circ-0000247) in the nine circRNAs was the most obvious one among the 3 groups, the area under the maximum curve was found by ROC curve analysis, SIGR=0. 802 5[ 95% confidence interval (0.665 5-0.939 5), P=0.001]; ST2DM=0.77[95% confidence interval (0.624-0.916), P=0.003]. In order to verify the clinical diagnostic ability of hsa-circ-000094, the experiment was conducted to further expand the sample ( n=150). The results showed that the expression of hsa-circ-000094 in the three groups was different, the difference and ROC curve analysis were statistically significant, SIGR=0. 673 3 [ 95% confidence interval (0.575 7-0. 771 0), P＜0. 01]; ST2DM=0. 723 1 [ 95% confidence interval ( 0. 632 7-0. 813 4), P＜ 0.01]. Conclusion The higher expression of hsa-circ-000094 in peripheral blood provides a certain diagnostic basis for pre-diabetes as well as type 2 diabetes mellitus.

Sepsis can cause life-threatening organ dysfunction and is one of the leading causes of death in critically ill patients. Early diagnosis and correct treatment of sepsis are the key to reducing the fatality, however, there is no golden standard for diagnosis at present. The ideal sepsis biomarker can be used for early diagnosis and predicting poor prognosis with good sensitivity and specificity. There are many candidate biomarkers for sepsis. This article reviews the latest developments on acute phase proteins, soluble receptors, non-coding RNAs and other candidate biomarkers of sepsis that attracted more recent attention.

The incidence of in-hospital death in acute myocardial infarction (AMI) is high, which seriously threatens the life and health of patients. At present, many countries and regions have established a variety of objective assessment models for predicting the in-hospital mortality of patients with AMI, providing important decision-making support for patients with different risk levels when formulating treatment plans. With the rise of artificial intelligence, many new modeling methods also show certain advantages over the traditional models. This article systematically introduces the commonly used and newly constructed risk prediction models for in-hospital mortality of AMI, in order to provide help for medical staff to assist decision-making in clinical practice, and provide reference for the establishment of a safe and more effective risk prediction model in the future.

Objective Nicotinamide phosphoribosyltransferase (Nampt) is a new therapeutic target for ischemic stroke. The aim of this study was to investigate protective effect of liver-derived Nampt on ischemic stroke. Methods Liver-specific Nampt knockout mice were generated using the Cre/loxP system. Nampt^loxP/loxP mice were crossed with liver-specific Cre recombinase expression mice (Alb-Cre), and the progeny genotypes were identified by polymerase chain reaction. Body weight of knockout mice and control mice were measured. Nampt in liver and brain was determined by Western blot assay. Middle cerebral artery occlusion (MCAO), a classical ischemic stroke model, was generated in liver-specific Nampt knockout mice and control mice by electrocoagulation. After 24 h of modeling, neurological deficit scores of each group were evaluated and TTC staining was performed to determine the cerebral infarction volume. The level of plasma Nampt in each group was determined by ELISA. Results Liver-specific Nampt knockout mice with the genotype of Nampt^loxP/loxPAlb-Cre were successfully constructed. The hepatic Nampt expression in knockout mice was significantly decreased by 74.2% compared to control mice, while there was no significant difference in the expression of brain Nampt protein between the knockout group and the control group. Specific knockout of liver Nampt gene expression had no effect on the body weight of mice. Under normal physiological conditions, there was no significant difference in plasma Nampt levels between liver-specific Nampt knockout mice and control mice of the same gender. 24 h after MCAO modeling, there were no significant differences in neurological deficit scores, cerebral infarct volume and plasma Nampt concentration between liver-specific Nampt knockout group and control group. Conclusion Liver-specific Nampt knockout mice are successfully constructed. Liver-derived Nampt has no significant protective effects on ischemic stroke.

Objective: To compare the efficacy between chemotherapy plus granulocyte colony-stimulating factor (G-CSF) and chemotherapy plus G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood stem cells (PBSC) and hematopoietic recovery after transplantation in patients with multiple myeloma (MM). Methods: A retrospective study of autologous PBSC (APBSC) mobilization data of 56 MM patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to July 2016 in Tianjin Medical University Cancer Institute and Hospital was conducted. The mobilization efficacy and hematopoietic recovery were analyzed. Results: In the univariate analysis, the successful collection rate of a single harvest in women and in patients with ISS stage Ⅲ and R-ISS stage Ⅱ/Ⅲ and treated with chemotherapy plus G-CSF was lower (P<0.05). However, age (≤60 years vs.>60 years), subtype, D-S staging (Ⅰ+Ⅱvs.Ⅲ), number of cycles of chemotherapy before mobilization (≤6 cycles vs.>6 cycles), disease phase before mobilization (PR vs. CR), and interval between diagnosis and mobilization (≤18 months vs.>18 months) were not correlated with CD34+ cell collection and successful mobilization rates (P>0.05). In the multivariate model, the successful mobilization rate in patients who received the chemotherapy plus G-CSF and GM-CSF mobilization regimen was higher (OR=12.009, 95% CI=1.961-73.537). The effect of mobilization regimens remained significant (P=0.007). Hematopoietic recovery without transplantation-related mortality occurred successfully in all patients. Conclusions: Chemotherapy plus G-CSF and GM-CSF mobilization regimens can significantly increase the effect of APBSC mobilization and ensure the recovery of hematopoietic function after transplantation. Chemotherapy plus G-CSF and GM-CSF mobilization regimens are safe and effective for mobilizing APBSCs.

Objective:To illustrate the effect and mechanism of ibrutinib,a Bruton's tyrosine kinase(BTK)inhibitor that inhibits diffuse large B-cell lymphoma(DLBCL)cell survival.Methods:DLBCL cell lines SUDHL-10 and HBL-1 were treated with ibrutinib at different concentrations.A MTT assay was used to detect the inhibition of cell proliferation.Cell apoptosis was analyzed by Annexin V-binding assay,as well as flow cytometry and DAPI staining.The expression of phosphorylated BTK,AKT and ERK was detected by Western blot. DLBCL cells were co-cultured with MSC.The inhibitory effect of ibrutinib on DLBCL cells in tumor microenvironment was assessed in clonogenicity in vitro and in a tumor-bearing non-obese diabetic/severe combined immunodeficient mice in vivo.Results:Up to 2.5 μmol/L and high concentrations of ibrutinib significantly inhibited the proliferation of DLBCL cells in a dose-dependent manner.Approx-imately 1 and 2.5 μmol/L ibrutinib was added on SUDHL-10 cells for 24 h,and the cell apoptotic rates were(21.73±3.64)% and(34.71± 2.36)%,respectively.Both were superior to that of the control group(3.55±1.89)%(P<0.05).Both two DLBCL cell lines pretreated with 5 and 10 μmol/L ibrutinib for 24 h and exhibited nuclear shrinkage at 5 μmol/L and nuclear fragmentation at 10 μmol/L.The expres-sion of phosphorylated BTK,AKT,and ERK decreased significantly after ibrutinib treatment.Ibrutinib inhibited clonogenicity in vitro(P<0.01)and cell proliferation and growth in vivo of DLBCL cells in co-culture system.The differences were statistically significant.Conclu-sion:Ibrutinib can inhibit the proliferation and induce apoptosis of SUDHL-10 and HBL-1 cell lines through a mechanism of blocking the AKT and ERK signaling pathways,as well as the proliferation of DLBCL cells in tumor microenvironment.This finding can significant-ly benefit DLBCL treatment.