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Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.
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Objective To observe the clinical effect of traditional Chinese medicine inflammatory mixture on vascular endothelial cell injury, mcrocirculation disorder and organ dysfunction in sepsis. Methods 73 patients with sepsis were randomly divided into two groups: Anti-inflammatory mixture-treated group (40 cases) and control group (33 cases). Routine medicine therapy was given in both groups.Additionally, in the Anti-inflammatory mixture-treated group, 100 ml Anti-inflammatory mixture was given By oral or nasal feeding, every 12 hours for consecutive 7 days. Vascular endothelial injury index (Soluble thrombomodulin,Vascular endothelial growth factor-2, endothelial specific molecule-1), mcrocirculation disorder index (arterial blood lactate, central venous oxygen saturation, total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index) of two group patients before and after therapy were observed and the sequential organ failure score (SOFA) was recorded before and after treatment. Results After treatment, the indexes of vascular endothelial injury sTM (12.37 ± 5.08 μg/L vs. 18.77 ± 6.88 μg/L, t=3.448), VEGF-2 [45.6 ng/L (14.3, 112.5) vs. 52.4 ng/L (17.2, 123.6), Z=4.009], ESM-1 (15.54 ± 4.09 ng/ml vs. 17.64 ± 6.79 ng/ml, t=-1.551), Lac (2.6 ± 1.2 mmol/L vs. 3.7 ± 1.8 mmol/L, t=4.115) and SOFA (4.1 ± 1.7 vs. 6.1 ± 3.2, t=-2.118) in anti-inflammatory mixture group decreased significantly than those in the control group. but the ScvO2(0.719 ± 0.243 vs. 0.603 ± 0.201, t=-2.773), PVD (14.8 ± 5.8 mm/mm2 vs. 13.1±5.1 mm/mm2, t=-5.114), PPV (59.1% ± 22.5% vs. 53.9% ± 20.6%, t=1.779), MFI (9.4 ± 4.6 vs. 7.2 ± 2.2, t=4.339) in the anti-inflammatory mixture group were significantly higher than those in the control group. Correlation analysis showed that the sTM and PPV were significantly negatively correlated (r=-0.875, P＜0.01), ESM-1 was significantly negatively correlated with PVD, PPV and MFI (r=-0.877, P＜0.01; r=-0.799, P＜0.01; r=-0.821, P＜0.01) and ESM-1 and SOFA were significantly positively correlated (r=0.840, P＜0.01). Conclusions Anti-inflammatory mixture of Chinese medicine has a certain therapeutic effect on sepsis by protecting vascular endothelial cell function.
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AIM:To investigate the effect of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) on the Notch signaling pathway in a model of oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) damage.METHODS:HUVECs were divided into control group, ox-LDL group, DAPT group and ox-LDL+DAPT group.The morphological changes of the HUVECs with different treatments were observed under light microscope.The viability of the HUVECs was measured by CCK-8 assay.The protein expression levels of Notch1, Notch4 and Jagged1 were determined by Western blot.RESULTS:ox-LDL induced great damage to the HUVECs, evidenced by increased cell death and debris in the culture.However, the cell damage was abolished by adding DAPT into the culture.The viability of the HUVECs was increased by co-treatment with DAPT and ox-LDL.ox-LDL treatment significantly decreased the protein expression levels of Notch1 and Jagged1, and elevated Notch4.However, these changes were totally reversed by DAPT.None of these proteins showed significant change in the HUVECs co-treated with DAPT and ox-LDL as compared with control group.CONCLUSION:ox-LDL is able to induce HUVEC damage in vitro.DAPT attenuates ox-LDL-induced damage in the HUVECs by regulating the Notch signaling pathway.
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Objective To observe the clinical therapeutic effect of Xuebijing injection on vascular endothelial cell ( VEC) injury,microcirculation disorder and organ dysfunction in patients with sepsis. Methods Seventy?three patients with sepsis were randomly divided into two groups:Xuebijing injection?treated group (40 cases) and control group (33 cases). Routine medicine therapy was applied in both groups. Additionally, the Xuebijing injection?treated group was treated with Xuebijing injection 100 ml and saline 100 ml by intravenous drip every 12 hours for consecutive 5 days. Vascular endothelial injury index, including soluble thrombomodulin( sTM) ,vascular endothelial growth factor 2 ( VEGF?2) ,endothelial specific molecule 1 ( ESM?1),microcirculation index of arterial blood lactic acid (Lac),central venous oxygen saturation (ScvO2),total microvessel density (TVD),the perfusion vascular density (PVD),proportion of perfused vessels (PPV) and microvessel flow index ( MFI) of the two groups before and after therapy were observed and the sequential organ failure score ( SOFA) was recorded before and after treatment. Results Senventy?three patients with sepsis had different degrees of increase in vascular endothelial damage markers,lactate and sequential organ failure scores in arterial blood, while the central venous blood oxygen saturation ( ScvO2 ) , the total vascular density of the sublingual microvasculature ( TVD) ,perfused vessel density ( PVD) ,proportion of perfused vessels ( PPV) and microcirculatory flow index ( MFI) decreased before treatment. After 5?day treatment,the above indicators of all patients were improved,the indexes in the Xuebijing injection group decreased significantly,compared with the control group ,sTM ( (16. 91±4. 55) μg/L,(19. 51±4. 09) μg/L,t=-6. 021,P<0. 05),VEGF?2 (50. 8 (17. 8,127. 7) ng/L vs. 74. 9(22. 7,155. 1) ng/L,t=4. 227,P<0. 05),ESM?1 ( (10. 20 ±2. 43) μg/L vs. (14. 80±3. 52) μg/L,t=-4. 113,P<0. 05),Lac( (2. 1±0. 7) mmol/L vs. (3. 7±1. 1) mmol/L,t=2. 366,P<0. 05) and SOFA ( (5. 9±2. 1) vs. (8. 7±2. 6),t=-7. 990,P<0. 05). ScvO2( (0. 771±0. 153) % vs. (0. 641±0. 113) %,t=5. 061,P<0. 05),PVD ( (16. 8±6. 1) mm/mm2 vs. (12. 1±5. 1) mm/mm2,t=4. 002, P<0. 05),PPV ( (66. 2±21. 3) % vs. (50. 4±19. 3) %,t=-2. 550,P<0. 05) and MFI (6. 2 ±2. 4) vs. (3. 8 ±2. 2),t=-5. 001,P<0. 05) were significantly higher than those in the control group in the same period. sTM and PPV had a significant negative correlation (r=-0. 755,P=0. 000),PVD,PPV,ESM?1 and MFI were negatively correlated (r=-0. 665,P=0. 000; r=-0. 600,P=0. 000; r=-0. 469,P=0. 000),PPV,MFI and SOFA were negatively correlated ( r=-0. 798,P=0. 000;r=-0. 995,P=0. 000);sTM,ESM?1 and SOFA were significantly positively correlated ( r = 0. 883, P = 0. 000;r = 0. 881, P = 0. 000 ) . Conclusion Vascular endothelial cell dysfunction probably plays an important role in the pathophysiology of sepsis and Xuebijing injection has therapeutic effect on sepsis by protecting vascular endothelial cell function.
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The oxidative response of Bacillus sp F26 to different forms of reactive oxygen species (ROS) stress including H2O2, O2- * and OH * were investigated by using diverse generating source of ROS, which were characterized by synthesis of antioxidative enzymes. It was shown that the responses of cells to oxidative stress are largely dependent on species, mode (instantaneous and continual) and intensity of stress. Higher synthesis rate of catalase (CAT) is crucial for Bacillus sp F26 to resist H2O2 stress. The damage of H2O2 to cell was minor if CAT can efficiently decompose H2O2 entering into cell, furthermore, the response can stimulate cell growths and sugar consumption. Conversely, cell growth and synthesis of antioxidative enzymes are greatly inhibited when the intensity of H2O2 stress overwhelms the cell capability of clearing H2O2. Due to the difference in mode and effect on cells between O2- * and H2O2, higher synthesis rates of CAT and superoxide dismutase (SOD) couldn't guarantee cells to eliminate H2O2 and O2- * efficiently. Therefore, the toxicity to cells induced by intracellular O2- * is more severe than H2O2 stress. Unlike response to H2O2 and O2- *, OH stress significantly inhibited cell growth and synthesis of antioxidative enzymes due to the fact OH * is most active ROS. Our results indicated that Bacillus sp F26 will show diverse biological behaviour in response to H2O2, O2- * and OH * of stress due to the discrepancy in chemical property. In order to survive in oxidative stress, cells will timely adjust their metabolism to adapt to new environment including regulating synthesis level of antioxidative enzymes, changing rates of cells growth and substrate consumption.