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Objective To investigate the therapeutic effect of Yudantong decoction in mice with α-naphthyl isothiocyanate (ANIT)-induced cholestasis, as well as its targets and mechanism based on intestinal flora and intestinal barrier function. Methods A total of 24 C57BL/6 mice were randomly divided into control group, model group, Yudantong decoction group (YDTF group), and ursodeoxycholic acid (UDCA) group, with 6 mice in each group. The mice in the model group, the YDTF group, and the UDCA group were given ANIT 35 mg/kg/day by gavage on days 1, 4, 7, 10, and 13, and those in the YDTF group and the UDCA group were given Yudantong decoction or UDCA by gavage for 15 consecutive days; related samples were collected on day 16. Liver histopathology was observed, and liver function parameters were measured; immunohistochemistry was used to measure the protein expression levels of caspase-1, interleukin-1β (IL-1β), and FXR in the liver, and flow cytometry was used to measure the percentages of CD11b + , CD86 + , and CD45 + immune cells in the liver; 16S rDNA sequencing and information analysis were performed for fecal microorganisms; immunohistochemistry was used to measure the protein expression of the intestinal FXR/NLRP3 pathway, and immunofluorescence assay was used to measure the protein expression of intestinal E-cadherin and occludin. A one-way analysis of variance was used for comparison of continuous data with homogeneity of variance between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Welch test was used for comparison of data with heterogeneity of variance between multiple groups, and the Games-Howell test was used for further comparison between two groups. Results HE staining showed that the model group had partial hepatocyte fatty degeneration, massive necrosis of hepatocytes in hepatic lobules, damage of lobular structure, and massive inflammatory cell infiltration, and the YDTF group and the UDCA group had alleviation of hepatocyte fatty degeneration and hepatocyte necrosis in hepatic lobules, with a reduction in inflammatory cells. Compared with the control group, the model group had significantly higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and total bile acid (TBA) (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the serum levels of ALT, AST, GGT, ALP, TBil, DBil, and TBA (all P < 0.05), and the UDCA group had significant reductions in the serum levels of GGT, TBil, DBil, and TBA (all P < 0.05). Compared with the control group, the model group had significant increases in the levels of caspase-1 and IL-1β and a significant reduction in the expression of FXR in the liver (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the levels of caspase-1 and IL-1β in the liver and the UDCA group had a significant reduction in the level of IL-1β in the liver, and both the YDTF group and the UDCA group had a significant increase in the expression level of FXR in the liver (all P < 0.05). The model group had a significant change in the composition of intestinal flora compared with the control group ( P < 0.05); there was a significant difference in the structure of intestinal flora between the YDTF group and the model group ( P < 0.05), and there was also a significant difference in the composition of intestinal flora between the UDCA group and the control/model groups ( P < 0.05). Compared with the control group, the model group had a significant increase in the abundance of intestinal Akkermansia muciniphila and a significant reduction in the abundance of Lactobacillus johnsonii (both P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant reduction in the abundance of intestinal Akkermansia muciniphila , and the YDTF group had a significant increase in the abundance of Lactobacillus murinus , while the UDCA group had significant increases in the abundance of Lactobacillus murinus and Bifidobacterium pseudolongum (all P < 0.05). Compared with the control group, the model group had a significant reduction in the protein expression of intestinal FXR, a significant increase in the protein expression of intestinal NLRP3, and significant reductions in the expression of intestinal E-cadherin and occludin (all P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant increase in the protein expression of intestinal FXR, a significant reduction in the protein expression of intestinal NLRP3, and significant increases in the expression of intestinal E-cadherin and occludin (all P < 0.05). Conclusion Yudantong decoction can alleviate liver injury in mice with ANIT-induced cholestasis, possibly by improving intestinal flora and enhancing intestinal barrier function.
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Sepsis is the main cause of death in intensive care unit (ICU). Sepsis and septic shock seriously affect the prognosis of patients and increase the mortality and re-morbidity of patients. Early and timely intervention can reduce the mortality and recurrence rate of patients with sepsis. The occurrence of sepsis may be related to the phosphorylation of connexin 43 (Cx43), which needs to be realized through various signal pathways. The related sites of connexin 43 are phosphorylated through different signal pathways to achieve the precise regulation of sepsis, these sites may be related targets for the treatment of sepsis and provide a direction for accurate treatment of sepsis. This paper mainly analyzes the role of Cx43-related signal pathways such as protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the pathogenesis of sepsis.
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Objective@#To investigate the effect of mechanical ventilation in prone position combined with lung recruitment on severe acute respiratory distress syndrome (ARDS).@*Methods@#From February 2015 to February 2017, 82 patients with ARDS admitted to ICU of the Second Hospital of Shanxi Medical University were divided into two groups according to random number table, with 41 cases in each group.The study group was treated with mechanical ventilation in prone position combined with lung recruitment therapy, and the control group was treated with mechanical ventilation in supine position combined with lung recruitment therapy.The differences of heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), plateau pressure (Pplat), and static pulmonary compliance (Cst) were compared between the two groups before treatment (T0), and 1h (T1), 2h (T2), 6h (T3) after treatment.@*Results@#The PaO2 and PaO2/FiO2 levels of the two groups increased significantly after lung recruitment.In the study group at different time after treatment, PaO2[(69.17±7.51)mmHg, (74.64±6.78)mmHg, (82.52±10.37)mmHg], PaO2/FiO2 [(116.91±15.57)mmHg, (123.06±16.34)mmHg, (135.23±18.41)mmHg]were higher than those in the control group[PaO2: (64.23±7.72)mmHg, (68.51±8.05)mmHg, (73.43±9.12)mmHg; PaO2/FiO2: (106.50±12.97)mmHg, (115.42±13.19)mmHg, (123.42±14.95)mmHg], the differences were statistically significant (t=3.225, 3.254, 4.245, 3.954, 3.886, 4.135, all P<0.05). HR and CVP increased at T2-T3, T3 decreased, MAP decreased at T2-T3, and T3 increased in both two groups.HR at T1-T3 in the study group were (123.17±13.41)times/min, (114.64±10.08)times/min, (102.52±6.57)times/min, which were lower than those in the control group[(129.23±12.75)times/min, (117.51±10.35)times/min, (108.43±9.77)times/min], the differences between the two groups were statistically significant (t=3.884, 4.215, 4.667, all P<0.05).@*Conclusion@#Prone position mechanical ventilation combined with lung recruitment can effectively improve the oxygenation status of severe ARDS, and has less effect on hemodynamics, and the effect is better than supine position mechanical ventilation combined with lung recruitment.
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Objective To investigate the effect of mechanical ventilation in prone position combined with lung recruitment on severe acute respiratory distress syndrome (ARDS).Methods From February 2015 to February 2017,82 patients with ARDS admitted to ICU of the Second Hospital of Shanxi Medical University were divided into two groups according to random number table,with 41 cases in each group.The study group was treated with mechanical ventilation in prone position combined with lung recruitment therapy,and the control group was treated with mechanical ventilation in supine position combined with lung recruitment therapy.The differences of heart rate (HR),central venous pressure (CVP),mean arterial pressure (MAP),partial pressure of oxygen (PaO2),oxygenation index (PaO2/FiO2),plateau pressure (Pplat),and static pulmonary compliance (Cst) were compared between the two groups before treatment (T0),and 1h (T1),2h (T2),6h (T3) after treatment.Results The PaO2 and PaO2/FiO2 levels of the two groups increased significantly after lung recruitment.In the study group at different time after treatment,PaO2 [(69.17 ±7.51) mmHg,(74.64 ±6.78) mmHg,(82.52 ± 10.37) mmHg],PaO2/FiO2 [(116.91 ±15.57) mmHg,(123.06 ± 16.34) mmHg,(135.23 ± 18.41) mmHg] were higher than those in the control group [PaO2:(64.23 ± 7.72) mmHg,(68.51 ± 8.05) mmHg,(73.43 ± 9.12) mmHg;PaO2/FiO2:(106.50 ± 12.97) mmHg,(115.42 ± 13.19) mmHg,(123.42 ± 14.95) mmHg],the differences were statistically significant (t =3.225,3.254,4.245,3.954,3.886,4.135,all P ＜ 0.05).HR and CVP increased at T2-T3,T3 decreased,MAP decreased at T2-T3,and T3 increased in both two groups.HR at T1-T3 in the study group were (123.17 ± 13.41) times/min,(114.64 ± 10.08) times/min,(102.52 ± 6.57) times/min,which were lower than those in the control group [(129.23 ±12.75) times/min,(117.51 ± 10.35) times/min,(108.43 ± 9.77) times/min],the differences between the two groups were statistically significant (t =3.884,4.215,4.667,all P ＜ 0.05).Conclusion Prone position mechanical ventilation combined with lung recruitment can effectively improve the oxygenation status of severe ARDS,and has less effect on hemodynamics,and the effect is better than supine position mechanical ventilation combined with lung recruitment.
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BACKGROUND:Bone marrow mesenchymal stem cels have a therapeutic effect on acute lung injury, but the mechanism is unclear. If the mechanism is understood, the majority of patients with acute lung injury can obtain a benefit. OBJECTIVE:To explore the possible mechanism underlying bone marrow mesenchymal stem cels in the treatment of acute lung injury with sepsis in rats. METHODS: (1) Thirty-six adult Wistar rats were randomly divided into three groups, sham operation group (sham group), sepsis group and bone marrow mesenchymal stem cels group (cel treatment group). In the sepsis and cel treatment groups, animal models of sepsis with acute lung injury were established by cecal ligation and puncture, while in the sham group, the cecum was not ligated and punctured. Then, 1 mL normal saline was injected via the femoral vein in the sepsis and sham groups, and 1 mL bone marrow mesenchymal stem cel suspension (1×109/L) was injected into the cel treatment group. After 6 hours, interleukin 10 and macrophage inflammatory protein-2 levels in serum were measured in the three groups. Lung tissues were taken for pathological observation using hematoxylin-eosin staining. (2) Rat alveolar macrophages were obtained by bronchoalveolar lavage, seeded into 24-wel culture plates, and divided into three groups: control group (group A), sepsis model group (group B) and intervention group of bone marrow mesenchymal stem cels (group C). Normal saline, septic plasma, and co-intervention of septic plasma and mesenchymal stem cels were used in the groups A, B, C, respectively. Then, cels in the three groups were cultured in a 5% CO2 incubator at 37℃ for 1 hour. After that, alveolar macrophages were taken to detect whether nuclear factor-κB (P65) protein entered into the nucleus using laser scanning confocal microscopy. RESULTS AND CONCLUSION: (1) The results of animal experiments showed that compared with the sham group, the macrophage inflammatory protein-2 levels in the sepsis group and cel treatment group were significantly increased (P 0.05); inflammatory cel infiltration, interstitial pulmonary edema and pulmonary hemorrhage existed in the sepsis and cel treatment groups, but these symptoms were significantly reduced in the cel treatment group compared with the sepsis group. (2) Results from cel experiments showed that compared with the group A, in group B and group C, the number of nuclear factor-κB (P65) proteins into the nucleus was significantly higher (P < 0.05), but it was lower in the group C than the group B (P < 0.05). These findings indicate that bone marrow mesenchymal stem cels in acute lung injury with sepsis can regulate nuclear factor-κB (P65) protein of alveolar macrophages into the nucleus, reduce expression of macrophage inflammatory protein-2, and thereby play a protective role in the lungvia reducing neutrophil infiltration. Temporarily, this study cannot explain whether bone marrow mesenchymal stem cels have an effect on interleukin 10.
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Objective To study the efficacy and side effects of Ganciclovir combined with L-ornithine-L-aspartate on infant cytomegalovirus(CMV) hepatitis.Methods Sixty infants with CMV hepatitis hospitalized in our hospital from Dec.2009 to Dec.2010 were treated with ganciclovir combined with L-ornithine-L- aspartate.The parameters observed in the study included the pre-and post-treatment data on total Bilirubin (TBIL),alanine aminotransferase (ALT),alkaline Phosphatase (AKP)and the retraction of liver and spleen,as well as the adverse reactions of the treatment.Results The treatment significantly decreased serum TBIL (t =5.74,P ＜ 0.05 ),ALT( t =2.92,P ＜ 0.05 ) and liver( t =8.27 P ＜ 0.05 ) and spleen volume ( t =5.03,P ＜0.05).However,side effects such as liver damage and rash occurred occasionally during the ganciclovir treatment.Intravenous infusion of L-omithine-L-aspartate caused side effects such as vomiting and other mild gastrointestinal reactions.Conclusion The treatment of Ganciclovir combined with L-ornithine-L-aspartate on infant cytomegalovirus hepatitis created good efficacy and can be considered as the first treatment choice.Though it is relatively safe,adverse reactions should be monitored during the treatment.