1.Preparation of chrysin-phospholipid complex and its pharmacokinetic behaviors
Xiaoge CUI ; Lingli CAO ; Jiawei HOU ; Jiaojiao WANG ; Haijun HAO ; Jianxin WANG
Chinese Traditional Patent Medicine 2017;39(5):934-939
AIM To prepare the chrysin-phospholipid complex and to investigate its pharmacokinetic behaviors.METHODS Solvent evaporation method was used for preparing the complex.With preparation temperature,preparation time,chrysin concentration and drug-lipid ratio (chrysin-phospholipid) as influencing factors,together with recombination rate as an evaluation index,the preparation was optimized by orthogonal test.The obtained complex was analyzed by X-ray diffraction,differential scanning calorimetry,1H-NMR and 31P-NMR,whose solubility was examined as well.SD rats were intragastrically administered with chrysin and its phospholipid complex,respectively.The blood concentration of chrysin was detected by HPLC,after which the pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 40 ℃ for preparation temperature,2 h for preparation time,20 mg/mL for chrysin concentration,and 1 ∶ 2 for drug-lipid ratio,the recombination rate was close to 100%.Chrysin existed in an amorphous state in the phospholipid complex,which was a new phase rather than physical mixture (chrysin-phosphatidylcholine),and no new chemical bond was generated.Phospholipid complex could significantly increase chrysin's apparent solubility in water and n-octanol,the Cmax,AUC0-t and AUC0-∞ were also obviously increased as compared with raw medicine.CONCLUSION Phospholipid complex can improve both the solubility of chrysin and its oral bioavailability.
3.Effect of rat bone marrow mesenchymal stem cells on dynamic changes of inflammatory factors and apoptosis index during hepatocarcinogenesis
Qingqin ZHANG ; Xiaoge KOU ; Yanhui CUI ; Luonan WANG ; Cailing JIN ; Meiling CHEN ; Weiwei LI
Chinese Journal of Tissue Engineering Research 2016;20(36):5358-5363
BACKGROUND:Bone marrow mesenchymal stem cel transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cel s and inflammatory factor level.
OBJECTIVE:To investigate the effect of rat bone marrow mesenchymal stem cel s on dynamic change of inflammatory factors and cel apoptosis during hepatocarcinogenesis.
METHODS:Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cel transplantation via the tail vein. Two weeks after cel transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1αdetected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cel apoptosis index detected by TUNEL technique.
RESULTS AND CONCLUSION:After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P<0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cel transplantation (P<0.05) and close to the normal levels (P>0.05). Bone marrow mesenchymal stem cel transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1αin the liver tissue that was decreased obviously after modeling (P<0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P<0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cel s.
4.Analysis of lymphocyte subsets in patients with sepsis and its impact on prognosis.
Hongfu YANG ; Pingna LI ; Qiumin CUI ; Ning MA ; Qilong LIU ; Xiaoge SUN ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(7):702-706
OBJECTIVE:
To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis.
METHODS:
The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis.
RESULTS:
(1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (μg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×109/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×109/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/μL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3+ absolute value (pieces/μL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3+CD4+ absolute value (pieces/μL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19+ absolute value (pieces/μL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3+CD8+ absolute value (pieces/μL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/μL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/μL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4-CD8- absolute value (pieces/μL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4+CD8+ absolute value (pieces/μL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis.
CONCLUSIONS
The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.
Humans
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Male
;
Adolescent
;
Retrospective Studies
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ROC Curve
;
Sepsis/diagnosis*
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Lymphocyte Count
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Lymphocyte Subsets
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Prognosis
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Killer Cells, Natural
5.Predictive value of the maximum aggregation rate of platelet for septic shock and septic shock with disseminated intravascular coagulation
Qiumin CUI ; Xiaoge SUN ; Ning MA ; Qilong LIU ; Hongfu YANG ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(3):238-243
Objective:To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC).Methods:A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis.Results:A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×10 9/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×10 9/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95% CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95% CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score ( r = -0.327, P = 0.000). Conclusions:MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt alsocan be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.
6.Expression level of cytokines in patients with sepsis and its effect on prognosis.
Pingna LI ; Hongfu YANG ; Qiumin CUI ; Ning MA ; Qilong LIU ; Xiaoge SUN ; Rongqing SUN
Chinese Critical Care Medicine 2023;35(12):1250-1254
OBJECTIVE:
To observe the expression level of cytokines in patients with sepsis and its effect on prognosis.
METHODS:
The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis.
RESULTS:
(1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (μg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×109/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%.
CONCLUSIONS
APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.
Humans
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Male
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Interleukin-10
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Interleukin-17
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Cytokines
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Tumor Necrosis Factor-alpha
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Interleukin-6
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Retrospective Studies
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Interleukin-2
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Interleukin-4
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ROC Curve
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Sepsis/diagnosis*
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Prognosis
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Procalcitonin
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Interferon-gamma
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Intensive Care Units