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Objective To investigate the effect of Quzhi Ruangan prescription on the farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) pathway in rats with nonalcoholic steatohepatitis (NASH). Methods Male Sprague-Dawley rats were randomly divided into normal group (Control group with 8 rats), model group (HFD group with 12 rats), simvastatin group with 8 rats, high-dose Quzhi Ruangan prescription group (QH group with 8 rats), and low-dose Quzhi Ruangan prescription group (QL group with 8 rats). The rats in the Control group were fed with a normal diet and those in the other groups were fed with a high-fat diet. Related samples were collected at the end of week 10 to observe liver pathological changes and measure the serum levels of liver function parameters, the level of FGF19 in the liver and the small intestine, and the level of bile acid (BA) in the liver. The expression levels of FXR in the small intestine and cholesterol 7α-hydroxylase (CYP7A1) in the liver were also measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Compared with the Control group, the HFD group showed the pathological manifestations of marked inflammatory lesions and steatosis. Compared with the HFD group, all administration groups had a significant increase in high-density lipoprotein cholesterol and significant reductions in alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in FGF19 in the small intestine and a significant increase in BA in the liver (both P < 0.05). Compared with the HFD group, all administration groups had a significant increase in FGF19 in the small intestine and a significant reduction in BA in the liver (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the mRNA expression of FXR in the small intestine and a significant increase in the mRNA expression of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the QH group had a significant increase in the mRNA expression of FXR in the small intestine, while the QL group had a significant reduction (both P < 0.05), and the QH group had a significant reduction in the mRNA expression of CYP7A1 in the liver ( P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the positive rate of FXR in the small intestine and a significant increase in the positive rate of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the simvastatin group and the QH group had a significant increase in the positive rate of FXR in the small intestine (both P < 0.05), and the simvastatin group, the QH group, and the QL group had a significant reduction in the positive rate of CYP7A1 in the liver (all P < 0.05). Conclusion Quzhi Ruangan prescription can activate the FXR-FGF19 pathway in NASH rats and may exert a preventive and therapeutic effect on NASH through this pathway.
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Objective:To explore the value of radiographic assessment of lung edema (RALE) score in evaluating the severity and prognosis of patients with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted. Patients with ARDS admitted to the department of intensive care unit (ICU) of Affiliated Nantong Third Hospital of Nantong University from January 2016 to November 2020 were enrolled. Clinical data of those patients were collected, and two senior radiologists who did not know the outcome of the patients independently scored each chest radiograph, the mean value of which was taken as the RALE score. The patients were divided into death group and survival group according to the 28-day prognosis. The differences of the basic data, PaO 2/FiO 2, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and RALE score between groups were analyzed. ARDS patients were classified according to the Berlin standard and RALE scores were compared between groups. Then, the correlations between RALE score and PaO 2/FiO 2, SOFA score, APACHEⅡ score were analyzed. The prognostic capacity of RALE score for 28-day prognosis of ARDS patients were analyzed by Kaplan-Meier survival curve. Results:Of the 98 ARDS patients, 62 were included in the final analysis, 39 patients survived and 23 patients died. The 28-day mortality was 37.1%. Compared with the survival group, patients in the death group were older (years old: 72.83±12.21 vs. 64.44±14.68), had lower PaO 2/FiO 2 [mmHg (1 mmHg = 0.133 kPa): 122.66±48.32 vs. 150.26±50.40], and higher SOFA score and greater difference of RALE score between the third day and the first day after admission (D3-D1 RALE score) (SOFA score: 11.26±3.91 vs. 9.04±3.72, D3-D1 RALE score: 1.35±6.42 vs. -2.74±7.35), with statistically significant differences (all P < 0.05). However, there were no significant differences in gender, cause of ARDS, APACHEⅡ score, and RALE scores on the first and the third day of admission (D1 RALE, D3 RALE) between the two groups. Among the 62 patients, there were 11 mild cases (17.7%), 36 moderate cases (58.1%), and 15 severe cases (24.2%). The D1 RALE score of patients with mild and moderate ARDS were lower than those of patients with severe ARDS (19.09±3.65, 22.58±6.79 vs. 27.07±5.23, both P < 0.05). Correlation analysis showed that D1 RALE score was negatively correlated with PaO 2/FiO 2 ( r = -0.385, P = 0.002), and positively correlated with SOFA score and APACHEⅡ score ( r1 = 0.433, r2 = 0.442, both P < 0.001). Kaplan-Meier survival curve analysis showed that the 28-day survival rate of ARDS patients in D3-D1 RALE score ≥ -1 group was significantly higher than that in D3-D1 RALE score < -1 group (73.08% vs. 55.56%; log-rank test: χ 2 = 3.979, P = 0.046). Conclusions:The RALE score is a simple and reliable non-invasive evaluation index, which can be used to evaluate the severity of ARDS patients. The difference of RALE score in early stage is helpful to identify ARDS patients with poor prognosis.
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Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease (NAFLD) and can develop into life-threatening liver cirrhosis and liver cancer. Toll-like receptor 4 (TLR4) is a type of pattern recognition receptor in innate immunity, and after being activated, it can trigger a cascade reaction and activate nuclear factor-κB (NF-κB) which mediates inflammatory response. The TLR4/NF-κB signaling pathway is a classic inflammatory pathway. In clinical practice, traditional Chinese medicine has achieved a good effect in the treatment of NASH, and the TLR4/NF-κB signaling pathway is one of the approaches for traditional Chinese medicine to treat NASH. By searching the relevant literature, this article summarizes the active components and compounds of traditional Chinese medicine that can regulate the TLR4/NF-κB signaling pathway to alleviate NASH, so as to provide ideas for future research and medication.
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Objective:To investigate the risk factors of citrate accumulation in patients with liver failure treated with regional citrate anticoagulated continuous renal replacement therapy (RCA-CRRT).Methods:The clinical data of liver failure patients with RCA-CRRT admitted to department of intensive care unit (ICU) of Nantong Third People's Hospital from January 2017 to June 2020 were retrospectively analyzed. The selected patients were divided into citrate accumulation group and control group according to whether there was citrate accumulation (serum total calcium/free calcium ratio ≥ 2.4) during CRRT. The age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), mean arterial pressure (MAP), norepinephrine (NE) dose, blood lactic acid (Lac) concentration, liver function status, citrate dose, filter time and prognosis of the patients were compared between the two groups. Unconditional Logistic regression was used to analyze the risk factors for citrate accumulation.Results:Among 48 patients with RCA-CRRT and liver failure, 20 patients had citrate accumulation (accumulation group), and a total of 96 CRRTs were performed; the remaining 28 patients did not have citrate accumulation (control group), a total of 106 CRRTs were performed. There were no significant differences in age and APACHEⅡ score between the two groups. Compared with the control group, the MAP in the accumulation group was lower [mmHg (1 mmHg = 0.133 kPa): 66.9±13.6 vs. 86.4±8.3, P = 0.032], and the dosage of NE (μg/min: 16.3±8.4 vs. 5.9±2.8, P = 0.015) and lactic acid level (mmol/L: 4.89±1.45 vs. 2.98±0.87, P = 0.004) were higher, the damage of liver function was more serious [total bilirubin (TBil, μmol/L): 220.4±45.2 vs. 163.4±43.8, P = 0.012; Child-Pugh score: 12.0±2.5 vs. 8.8±1.4, P = 0.029; model for end-stage liver disease (MELD) score: 31.30±8.22 vs. 21.78±6.40, P = 0.041], hourly citric acid dosage (mmol/h: 27.4±6.9 vs. 19.3±4.9, P = 0.032) and total citric acid dosage (mmol: 3 393±809 vs. 1 819±502, P = 0.039) were higher. Although there were no significant differences in the length of ICU stay, total length of hospitalization stay and cost of hospitalization between the two groups, the 28-day mortality of the accumulation group was higher than that of the control group (60.0% vs. 28.6%, P = 0.039). Unconditional Logistic regression analysis showed that MAP [odds ratio ( OR) = 2.901, 95% confidence interval (95% CI) was 0.921-19.493, P = 0.019], NE dosage ( OR = 2.098, 95% CI was 1.923-12.342, P = 0.002), Lac level ( OR = 5.201, 95% CI was 3.211-9.433, P = 0.012), Child-Pugh score ( OR = 1.843, 95% CI was 0.437-7.420, P = 0.018), MELD score ( OR = 3.012, 95% CI was 0.384-12.843, P = 0.031), hourly citric acid dosage ( OR = 4.254, 95% CI was 1.734-11.839, P = 0.011) and total citric acid dosage ( OR = 4.109, 95% CI was 1.283-18.343, P = 0.001) were risk factors for citrate accumulation. Conclusion:In patients with tissue hypoperfusion and severe liver function damage, citrate anticoagulation should be avoided or the dosage of citric acid should be reduced, in order to avoid citrate accumulation.
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ObjectiveTo investigate the effect of Quzhi Ruangan decoction on the mRNA and protein expression of organic anion transporting polypeptide 2B1 (OATP2B1) in the small intestine of rats with nonalcoholic fatty liver disease (NAFLD). MethodsAfter 1 week of adaptive feeding, 36 male Sprague-Dawley rats were randomly divided into normal group, model group, simvastatin group, and high-, middle-, and low-dose Quzhi Ruangan decoction groups, with 6 rats in each group. Liver tissue was collected and HE staining was used to observe hepatic steatosis; an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), and cholesterol (CHOL); RT-PCR and Western blot were used to measure the mRNA and protein expression of OATP2B1 in the small intestine of rats. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results There were significant differences in liver index, GLU, and CHOL between groups (F=10.814, 12.298, and 5.024, all P＜0.05), and there were also significant differences in the mRNA and protein expression of OATP2B1 in the small intestine (F=13.384 and 73.025, both P＜0.05). Compared with the normal group, the model group had significant increases in the mRNA and protein expression of OATP2B1 (both P＜0.05); compared with the model group, the simvastatin group and the high- and middle-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (all P＜0.05); compared with the simvastatin group, the middle- and low-dose Quzhi Ruangan groups had a significant reduction in the mRNA expression of OATP2B1 (both P＜0.05). Compared with the normal group, the model group had a significant increase in the protein expression of OATP2B1 (P＜0.05); compared with the model group, all treatment groups had a significant reduction in the protein expression of OATP2B1 (all P＜0.001); compared with the simvastatin group, the high-, middle-, and low-dose Quzhi Ruangan groups had a significant reduction in the protein expression of OATP2B1 (all P＜0.05). ConclusionQuzhi Ruangan decoction may alleviate the pathological changes of NAFLD by reducing the overexpression of OATP2B1.
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Nonalcoholic steatohepatitis (NASH) is an important pathological stage of nonalcoholic fatty liver disease characterized by hepatocyte fatty degeneration, liver injury, and liver inflammation and can further develop into liver cirrhosis and hepatocellular carcinoma. The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a multi-protein complex in cells and can induce cell apoptosis and expand inflammatory response by activating caspase-1 and releasing mature inflammatory factors such as interleukin-1β and interleukin-18. Recent studies have found that NLRP3 inflammasome may participate in the development and progression of NASH. Therefore, this article summarizes the role of NLRP3 inflammasome in NASH, so as to provide a theoretical basis for future research and treatment.
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Objective To explore the clinical efficacy and safety of atorvastatin in the treatment of patients with septic shock.Methods 67 patients with septic shock were randomly divided into the treatment group (34 cases) and control group(33 cases).The control group was treated with conventional therapy ,and the observation group was administered with atorvastatin based on the control group .Before and after treatment ,the inflammatory index ,cytokines levels,the number of MODS cases,the number of deaths at 28th day,and the incidence of adverse reactions were com-pared between the two groups .Results The heart rate ,respiratory rate ,white blood cell count of the treatment group were significantly better than the control group ,the cytokines levels were significantly lower than the control group ,the differences were statistically significant (t=4.181,3.622,4.879,all P0.05).Conclusion Atorvastatin can effectively reduce the degree of inflammatory reaction in patients with septic shock ,decrease the incidence of MODS , and has potential benefits on the prognosis of patients , but still need to be further confirmed by clinical research .