Cathepsin B in hepatic Kupffer cells regulates activation of TLR4-independent inflammatory pathways in mice with lipopolysaccharide-induced sepsis / 南方医科大学学报

OBJECTIVE@#To investigate the role of cathepsin B in hepatic Kupffer cells (KCs) in activating Toll-like receptor 4(TLR- 4)-independent inflammatory pathways in mice with lipopolysaccharide (LPS)-induced sepsis.@*METHODS@#Eighteen wild-type (WT) mice and 18 TLR4-knockout (TLR4) mice were both divided into 3 groups for intraperitoneal injections of a lethal dose (54 mg/kg) of LPS, LPS and CA-074(a cathepsin B inhibitor), or normal saline, and the survival of the mice were observed. Another 36 WT mice and 36 TLR4mice were also divided into 3 groups and subjected to intraperitoneal injections of normal saline, 20 mg/kg LPS, or LPS with CA-074 pretreatment.After the treatments, KCs were collected from the mice for assessing the protein level and activity of cathepsin B.The histopathological changes of the liver were observed with HE staining, and the serum levels of IL-1α, IL-1β, TNF-α and IL-18 were detected.@*RESULTS@#Compared with the WT mice,TLR4mice receiving the lethal dose of LPS had significantly longer survival time (up to 84 h) after the injection,but were still unable to fully resist LPS challenge.CA-074 pretreatment prolonged the survival time of WT mice and TLR4mice to 60 h and 132 h,respectively.In the mouse models of sepsis,20 mg/kg LPS induced significantly enhanced activity of cathepsin B without affecting its expression level in the KCs (<0.05) and increased the serum levels of the inflammatory cytokines.CA-074 pretreatment of the mice obviously lessened the detrimental effects of LPS in TLR4mice by significantly lowering cathepsin B activity in the KCs,alleviating hepatocyte apoptosis and reducing the serum levels of inflammatory cytokines.@*CONCLUSIONS@#Cathepsin B plays an important role in activating TLR4-independent inflammatory pathways in mice with LPS-induced sepsis.

Effect of liraglutide in treatment of non-alcoholic fatty liver disease: mechanism of action and research advances / 中华肝脏病杂志

Non-alcoholic fatty liver disease is a common chronic liver disease closely associated with obesity, hyperlipidemia, and diabetes. It can gradually progress to liver cirrhosis or even hepatocellular carcinoma; however, there are still no specific therapeutic agents for this disease. Liraglutide is a human glucagon-like peptide-1 analogue and has a marked effect in the treatment of type 2 diabetes. At present, many studies indicate that liraglutide also has a certain therapeutic effect on non-alcoholic fatty liver disease during the treatment of type 2 diabetes, but its mechanism of action remains unknown. This article reviews the known mechanisms of action of liraglutide in the treatment of non-alcoholic fatty liver disease.

"Practice and exploration on ""organ-systems-based curriculum"" reform of cardiovascular sys-tem" / 中华医学教育探索杂志

Chongqing Medical University selected some five-year clinical medical undergradu-ates to set up the pilot class which was called 'clinician excellent class' and implemented the 'organ-systems-based curriculum' (OSBC) integration teaching reform on them. The OSBC teaching of the cardiovascular system breaks the traditional pattern, and carries on the comprehensive reorganization to the curriculum contents and the teaching personnel, and emphasizes the collective preparation, the new teaching method and the reasonable evaluation system. Although OSBC teaching of the cardiovas-cular system has made some achievements, but there are still many deficiencies need to reflect on and improve.

CHADS₂versus CHA₂DS₂-VASc scoring systems for predicting left atrial thrombus in patients with nonvalvular atrial fibrillation / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the correlation of CHADS₂and CHA₂DS₂-VASc scores for left atrial thrombus in patients with nonvalvular atrial fibrillation and the differences in the results between the two scoring systems.</p><p><b>METHODS</b>A total of 397 patients with nonvalvular atrial fibrillation were enrolled in this study. The CHADS₂and CHA2DS2-VASc scoring systems were used for evaluating the risk of left atrial thrombus and their differences in the scores and risk stratifications were compared. The correlation of CHADS₂ and CHA₂DS₂-VASc scores with left atrial thrombus was analyzed.</p><p><b>RESULTS</b>The average score of CHA₂DS₂-VASc was significantly higher than that of CHADS₂in these patients (1.37 ± 1.19 vs 0.63 ± 0.78, P<0.001). The proportion of high-risk group was significantly higher (P<0.001) while that of low-risk group significantly lower as stratified by CHA₂DS₂-VASc scores than by CHADS₂scores (P<0.001). Transesophageal echocardiography detected left atrial thrombus in 44 of the total patients. The prevalence of left atrial thrombus increased significantly with a higher risk stratification by CHADS₂or CHA₂DS₂-VASc scores (P<0.05). Univariate analysis showed that female gender, age ≥ 65 years, left atrium diameter ≥ 38 mm, left ventricular ejection fraction ≤ 40%, hypertension, diabetes, coronary heart disease, stroke history, CHADS₂≥ 2, and CHA₂DS₂-VASc ≥ 2 were all correlated with left atrial thrombus, but multivariate logistic analysis identified only CHA₂DS₂-VASc ≥ 2 as the independent risk factor for left atrial thrombus (OR=9.85, 95% CI: 2.178-44.542, P < 0.01).</p><p><b>CONCLUSION</b>The average score of CHA₂DS₂-VASc is higher than that of CHADS₂and has better predictive ability for left atrial thrombus.</p>

Anti-tumor effects of supernatant from B16 melanoma cells mixedly cultured with lymphocytes and macrophages in vitro / 肿瘤研究与临床

Objective To study the anti-tumor effects of mixed cultured B16 melanoma cells supernatant.Methods The supernatant from purely cultured B16 melanoma cells or mixedly cultured B16 melanoma cells with lymphocytes and macrophages at indicated time points were collected,respectively.The chemotaxis of the two different cell supernatants was determined by Boyden room method.The activation effects towards lymphocytes of the two different supernatants were determined by CCK-8 method.Results When the cells were mixed cultured for 0.5,1,2,4,8 and 12 h,the numbers of lymphocytes to travel from the upper well to the bottom well were (1.00±0.82) × 104,(7.00±1.63) × 104,(9.50±0.58) × 104,(11.25±2.36) ×104,(17.25±1.71) × 104 and (21.50±1.29) × 104,respectively.When the cells were purely cultured for 0.5,1,2,4,8 and 12 h,the numbers of lymphocytes to travel from the upper well to the bottom well were (0.00±0.00) ×104,(0.25±0.50) × 104,(1.75±0.96) × 104,(5.25±0.96) × 104,(5.75±1.26) × 104 and (10.75±3.20) × 104,respectively.The mixed cultured group showed higher chemotaxis effects towards lymphocytes in comparison with the purely cuhured one at the same points except for 0.5 h (P ＜ 0.05).The mixed cultured group showed higher activation effects towards lymphocytes in comparison with the purely cultured at the same points except for 0.5 and 1 h (P ＜ 0.05).Each group showed higher chemotaxis and activation effects towards lymphocytes when they were cultured for 12 h than the other time points (P ＜0.05).Conclusion The supernatant from mixed cultured cells shows much higher chemotaxis and activation effects towards lymphocytes to kill tumor cells.

Effect of the activation of lymphocyte between freeze-thaw tumor cell and the supernatant of tumorcell culture / 肿瘤研究与临床

Objective To compare the effect of freeze-thaw tumor cells and the supernatant from tumor cell culture on the activation of lymphocytes. Methods Malignant melanoma B16 cells were prepared as tumor cell vaccine and the supernatant from tumor cell culture was collected at different time point.Transwell method was used to determine the chemotaxis of lymphocyte attracted by freeze-thaw tumor cells and the supernatant from tumnor cell culture. The cytotoxic activity of lymphocyte was detected by CCK-8 method. Results Freeze-thaw tumor cells and the supernatant from more than 2 h of tumor cell culture were found to show chemotaxis of lymphocyte. The chemotaxis of tumor cell culture more than 4 h was stronger than freeze-thaw tumor cells. Each group of chemotactic lymphocytes demonstrated to have the activity of killing tumor cells. The ability of killing tumor cells induced by the tumor cell culture more than 4 h was stronger than that induced by freeze-thaw tumor cells.In a certain range,the ability of lymphocyte chemotaxis and activation were enhanced over time. Conclusion The chemotaxis and cytotoxic activation of lymphocyte induced by the supernatant from tumor cell culture for a certain time are stronger than those by freeze-thaw tumor cells. The supernatant from tumor cell culture can be used as tumor antigen to get better immune activation instead of the freeze-thaw tumor cells.

Exploring on the standardized training model for residents in the department of cardiology / 中华医学教育探索杂志

The standardized training is an indispensible stage for the improvement of residents' comprehensive quality and for the training of high-qualified talents.The article preliminarily explored the standardized training model for residents,which was in accordance with the characteristics of the department of cardiology mainly from four aspects:the set-up of reasonable training program,the training of practical skills,the training of humanistic quality and the training of life-long learning ability.