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Objective:To explore the efficacy and safety of low- and medium-dose of glucocorticoids in adult patients with acute respiratory distress syndrome (ARDS) through Meta-analysis and trials sequential analysis (TSA).Methods:Databases associated with adult ARDS treatment with low- and medium-dose glucocorticoids both in English and in Chinese were searched from PubMed, Medline, China Biology Medicine (CBM), Cochrane Library, CNKI, Wanfang Data and VIP, of which the search duration was from the establishment of the database to December 2020. Low-dose glucocorticoids were defined as methylprednisolone ≤ 1 mg·kg -1·d -1, and medium dose glucocorticoids were defined as methylprednisolone ≤ 2 mg·kg -1·d -1. According to the Cochrane Collaboration bias risk assessment tool, the quality of the included literature was evaluated, and the data were extracted. Meta-analysis and TSA were used to evaluate the effects of low- and medium-dose glucocorticoids on the hospital mortality, intensive care unit (ICU) mortality, and mechanical ventilation free time in ICU for 28 days, PaO 2/FiO 2, and the occurrence of nosocomial infections and hyperglycemia. Results:A total of 996 patients in 7 literatures were finally included, including 515 patients in the low- and medium-dose glucocorticoid group (hormone group) and 481 patients in the conventional treatment group (control group). The research quality of 7 literatures was relatively high. The results of Meta-analysis and TSA showed that, compared with the control group, the hospital mortality in the hormone group was significantly decreased [relative risk ( RR) = 0.77, 95% confidence interval (95% CI) was 0.66-0.89, P = 0.000 6], and mechanical ventilation free time in ICU for 28 days was significantly prolonged [standardized mean difference ( SMD) = 0.50, 95% CI was 0.36-0.65, P < 0.000 1]. Although Meta-analysis showed that the ICU mortality of the hormone group was significantly lower than that of the control group ( RR = 0.61, 95% CI was 0.38-0.99, P = 0.04), the TSA results showed that the cumulative Z value crossed the traditional threshold, but did not cross the TSA cut-off value, and the sample size did not reach required information size (RIS, n = 3 252), needed more research to confirm. Although Meta-analysis showed that PaO 2/FiO 2 in the hormone group was significantly higher than that in the control group ( SMD = 0.78, 95% CI was 0.13-1.43, P = 0.02), TSA showed that the cumulative Z value did not pass the traditional and TSA cut-off values. More research was needed for verification. Meta-analysis also showed that there was no significant difference in the incidence of new infection ( RR = 0.93, 95% CI was 0.74-1.17, P = 0.54) and the incidence of hyperglycemia ( RR = 1.11, 95% CI was 1.00-1.23, P = 0.05) between the hormone group and the control group. Conclusion:low- and medium-dose of glucocorticoids therapy can reduce the hospital mortality of adult ARDS patients and shorten the mechanical ventilation duration in ICU for 28 days, and low- and medium-dose of glucocorticoids therapy does not increase the risk of infection and hyperglycemia.
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Objective:To determine the effect of andrographolide (AD) on the expression of procoagulant and fibrinolytic inhibitory factors in rat type Ⅱ alveolar epithelial cells (AECⅡ) stimulated by lipopolysaccharide (LPS).Methods:The AECⅡ cells RLE-6TN in the logarithmic growth phase were divided into 5 groups: the normal control (NC) group, the LPS group, and the 6.25, 12.5, and 25 mg/L AD groups (AD 6.25 group, AD 12.5 group, AD 25 group). The NC group was cultured with RPMI 1640 conventional medium. In the LPS group, 5 mg/L LPS was added to the RPMI 1640 conventional medium for stimulation. Cells in the AD groups were treated with 6.25, 12.5, and 25 mg/L AD in advance for 1 hour and then given LPS to stimulate the culture. The cells and cell culture supernatant were collected 24 hours after LPS stimulation. The protein and mRNA expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibition-1 (PAI-1) in cells were detected by Western blotting and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The levels of procollagen Ⅲ peptide (PⅢP), thrombin-antithrombin complex (TAT), antithrombin Ⅲ (AT-Ⅲ) and activated protein C (APC) in the cell supernatant were detected by enzyme linked immunosorbent assay (ELISA).Results:Compared with the NC group, the protein and mRNA expressions of TF and PAI-1 in the LPS group were significantly increased, and the protein and mRNA expressions of TFPI were significantly reduced. At the same time, the levels of PⅢP and TAT in the cell supernatant were significantly increased, the levels of AT-Ⅲ, APC were significantly reduced. Compared with the LPS group, the protein and mRNA expressions of TF and PAI-1 in AD 6.25 group, AD 12.5 group, AD 25 group were significantly reduced [TF/GAPDH: 0.86±0.08, 0.45±0.04, 0.44±0.04 vs. 1.32±0.10, TF mRNA (2 -ΔΔCt): 2.59±0.25, 2.27±0.05, 1.95±0.04 vs. 4.60±0.26, PAI-1/GAPDH: 2.11±0.07, 1.45±0.04, 0.86±0.09 vs. 2.56±0.09, PAI-1 mRNA (2 -ΔΔCt): 3.50±0.22, 2.23±0.29, 1.84±0.09 vs. 6.60±0.27, all P < 0.05], while the protein and mRNA expressions of TFPI were significantly increased [TFPI/GAPDH: 0.78±0.05, 0.81±0.03, 0.84±0.07 vs. 0.36±0.02, TFPI mRNA (2 -ΔΔCt): 0.46±0.09, 0.69±0.07, 0.91±0.08 vs. 0.44±0.06, all P < 0.05]. Also the levels of PⅢP and TAT in the cell supernatant were significantly reduced, and the levels of AT-Ⅲ and APC were significantly increased [PⅢP (μg/L): 13.59±0.23, 12.66±0.23, 10.59±0.30 vs. 15.82±0.29, TAT (ng/L): 211.57±6.41, 205.69±4.04, 200.56±9.85 vs. 288.67±9.84, AT-Ⅲ (μg/L): 102.95±3.86, 123.92±2.63, 128.67±1.67 vs. 92.93±3.36, APC (μg/L): 1 188.95±14.99, 1 366.12±39.93, 1 451.15±29.69 vs. 1 145.55±21.07, all P < 0.05]. With the increase of the dose of AD, the above-mentioned promotion and inhibition effects became more obvious. In the AD 25 group, TF, PAI-1 protein and mRNA expressions decreased, TFPI mRNA expression increased, PⅢP level in the supernatant decreased and AT-Ⅲ, APC levels increased compared with AD 6.25 group, the difference was statistically significant, and the decrease of PAI-1 protein expression and PⅢP level in the supernatant were also statistically significant compared with AD 12.5 group. Conclusions:Andrographolide in the dose range of 6.25-25 mg/L can dose-dependently inhibit the expression and secretion of procoagulant and fibrinolytic inhibitor-related factors in AECⅡ cells RLE-6TN stimulated by LPS, and promote the secretion of anticoagulant factors. 25 mg/L has the most obvious effect.
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Objective:To observe the effects of berberine on procoagulant and fibrinolytic inhibitory factors produced by rat type Ⅱ alveolar epithelial cell (AECⅡ) induced by lipopolysaccharide (LPS).Methods:AECⅡ cells (RLE-6TN cells) were cultured in vitro, and the cells in logarithmic growth phase were collected. The cytotoxicity text of berberine was detected by cell counting kit-8 (CCK-8) to determine the drug concentration range according to inhibition concentration of half cells (IC 50). The RLE-6TN cells were divided into five groups, the cells in blank control group were cultured in DMEM; the cells in LPS group were stimulated with 5 mg/L LPS; and the cells in berberine pretreatment groups were pretreated with 20, 50 and 80 μmol/L berberine for 1 hour, and then were co-cultured with 5 mg/L LPS. The cells were collected after LPS induced for 24 hours. The protein and mRNA expression levels of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1) in the cells were detected by Western blotting and real-time fluorescence quantification reverse transcription-polymerase chain reaction (RT-qPCR). The levels of activated protein C (APC), precollagen Ⅲ peptide (PⅢP), thrombin-antithrombin complex (TAT) and antithrombin Ⅲ (ATⅢ) in the cell supernatant were measured by enzyme linked immunosorbent assay (ELISA). Results:According to the inhibition rate curve, the IC 50 of berberine on RLE-6TN cells was 81.16 μmol/L. Therefore, 20, 50 and 80 μmol/L were selected as the intervention concentration of berberine. Compared with the blank control group, the expression and secretion of procoagulant and fibrinolytic inhibitory factors were abnormal in RLE-6TN cells after LPS induced for 24 hours. The protein and mRNA expression levels of TF and PAI-1 in the LPS group were significantly increased, but the protein and mRNA expression levels of TFPI were significantly decreased. Meanwhile, the levels of APC and ATⅢ in the cell supernatant were significantly decreased, while the levels of PⅢP and TAT were significantly increased. After pretreatment with berberine, the abnormal expression and secretion of procoagulant and fibrinolytic inhibitory factors induced by LPS were corrected in a dose-dependent manner, especially in 80 μmol/L. Compared with the LPS group, the protein and mRNA expression levels of TF and PAI-1 in the berberine 80 μmol/L group were significantly decreased [TF protein (TF/GAPDH): 0.45±0.02 vs. 0.55±0.03, TF mRNA (2 -ΔΔCt): 0.39±0.08 vs. 1.48±0.11, PAI-1 protein (PAI-1/GAPDH): 0.37±0.02 vs. 0.64±0.04, PAI-1 mRNA (2 -ΔΔCt): 1.14±0.29 vs. 4.18±0.44, all P < 0.01] and those of TFPI were significantly increased [TFPI protein (TFPI/GAPDH): 0.53±0.02 vs. 0.45±0.02, TFPI mRNA (2 -ΔΔCt): 0.94±0.08 vs. 0.40±0.05, both P < 0.01]. Meanwhile, the levels of APC and ATⅢ in the cell supernatant were significantly increased [APC (μg/L): 1 358.5±26.0 vs. 994.2±23.1, ATⅢ (μg/L): 118.0±7.4 vs. 84.4±2.7, both P < 0.01], while those of PⅢP and TAT were significantly decreased [PⅢP (μg/L): 11.2±0.4 vs. 18.6±0.9, TAT (ng/L): 222.1±2.8 vs. 287.6±7.0, both P < 0.01]. Conclusions:Berberine could inhibit the LPS-induced expressions of procoagulant and fibrinolytic inhibitory factors in rat AECⅡ cells and promote the expressions of anticoagulant factors in a dose-dependent manner. Berberine may be a new therapeutic target for alveolar hypercoagulability and fibrinolysis inhibition in acute respiratory distress syndrome (ARDS).
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Objective:To explore the effect of small dose of low molecular weight heparin on the prognosis of elderly patients with severe pneumonia using systematic evaluation method.Methods:Databases including Wanfang data, VIP, CNKI, SinoMed, PubMed, Embase and Cochrane Library were searched for randomized controlled trial (RCT) studies about the comparison of conventional therapy and low molecular weight heparin on prognosis of elderly patients with severe pneumonia from the time of database establishment to August 2019. The patients in conventional treatment group were treated by improving ventilation, anti-infection, eliminating phlegm, relieving asthma and maintaining homeostasis while those in low molecular weight heparin group were subcutaneously injected with low molecular weight heparin of 4 000 U, once a day for 7 days. The patients' main outcomes included the oxygenation index (PaO 2/FiO 2) after 7 days of treatment, duration of mechanical ventilation, mortality in hospital, and secondary outcomes included acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and coagulation function after 7 days of treatment, the length of intensive care unit (ICU) stay, and incidence of bleeding. Data extraction and quality evaluation were conducted. The Meta-analysis of included studies that met the quality standards was performed using RevMan 5.3 software. Funnel diagram analysis was used to analyze the parameters with no less than 10 studies enrolled. Results:A total of 14 RCT studies were enrolled involving 1 173 elderly patients with severe pneumonia, among whom 590 received low molecular weight heparin while the other 583 received conventional therapy. All the included studies were well designed and of high quality. The results of Meta-analysis showed that compared with conventional therapy, small dose of low molecular weight heparin significantly elevated PaO 2/FiO 2 after 7 days of treatment [mean difference ( MD) = 19.25, 95% confidence interval (95% CI) was 16.88 to 21.61, P < 0.000 01], shortened the duration of mechanical ventilation ( MD = -48.88, 95% CI was -67.42 to -30.33, P < 0.000 01), and decreased mortality in hospital [odds ratio ( OR) = 0.40, 95% CI was 0.22 to 0.73, P = 0.003] and APACHEⅡ score after 7 days of treatment ( MD = -3.38, 95% CI was -3.94 to -2.83, P < 0.000 01), and shortened the length of ICU stay ( MD = -4.51, 95% CI was -5.75 to -3.27, P < 0.000 01). There was no significant difference in the changes of coagulation parameters after 7 days of treatment or the incidence of bleeding between low molecular weight heparin group and conventional therapy group [7-day thrombin time (TT): MD = 0.57, 95% CI was -0.15 to 1.28, P = 0.12; 7-day prothrombin time (PT): MD = 0.32, 95% CI was -0.35 to 0.98, P = 0.35; 7-day fibrinogen (FIB): MD = -0.17, 95% CI was -0.45 to 0.10, P = 0.22; incidence of bleeding: OR = 0.86, 95% CI was 0.36 to 2.07, P = 0.74]. The funnel diagram showed that there was publication bias of included 10 studies about APACHEⅡ score after 7 days of treatment. Conclusion:Small dose of low molecular weight heparin can improve the prognosis of elderly patients with severe pneumonia and it has no obvious side-effect on coagulation function.
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Objective@#To explore the therapeutic effect of Xuebijing on patients with acute paraquat poisoning (APP) by using systematic evaluation method.@*Methods@#PubMed, Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure (CNKI), VIP database (VIP) and China Biology Medicine (CBM) were searched using the computers to find the literatures published about the Xuebijing injection for the treatment of APP. Randomized controlled trials (RCT) were retrieved from the establishment of the database to August 2019. Patients in experimental group were treated with Xuebijing injection combined with conventional treatment, while the patients in control group were only given conventional treatment. The patients' outcome included the 14-day mortality, arterial oxygen saturation (SaO2) and incidence of pulmonary fibrosis. In addition, the 6-month survival rate, alanine aminotransferase (ALT), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups were compared. The literature data were extracted by two researchers independently, and the quality of the literatures was evaluated according to the Cochrane 5.1 handbook. The Meta-analysis was performed by using RevMan 5.3 software. The results stability of Meta-analysis was tested by sensitivity analysis. The publication bias was analyzed through drawing of funnel diagram.@*Results@#Twenty-seven RCT studies in total were enrolled, of which 26 were in Chinese and 1 was in English. A total of 1 429 patients were enrolled, among whom 726 were in experimental group and another 703 were in control group. Meta-analysis showed that compared with the control group, the 14-day mortality [relative risk (RR) = 0.62, 95% confidence interval (95%CI) was 0.54 to 0.72, P < 0.000 01] and incidence of pulmonary fibrosis (RR = 0.67, 95%CI was 0.53 to 0.85, P = 0.000 9) of patients in the experimental group were significantly lowered, while SaO2 at 7 days and 14 days were significantly increased [7 days: mean difference (MD) = 16.86, 95%CI was 9.89 to 23.83, P < 0.000 01; 14 days: MD = 16.51, 95%CI was 10.22 to 22.80, P < 0.000 01]. Compared with the control group, the survival rate within 6 months (RR = 1.55, 95%CI was 1.41 to 1.71, P < 0.000 01) and SOD (MD = 13.88, 95%CI was 7.43 to 20.33, P < 0.000 1) of patients in the experimental group were significantly increased, ALT at 14 days (MD = -78.35, 95%CI was -127.35 to -29.34, P = 0.000 5), SCr at 7 days and 14 days (7 days: MD = -135.13, 95%CI was -219.09 to -51.17, P = 0.002; 14 days: MD = -206.05, 95%CI = -290.13 to -121.96, P < 0.000 01), CRP (MD = -11.55, 95%CI was -17.77 to -5.33, P = 0.000 3), TNF-α (MD = -9.27, 95%CI was -15.48 to -3.96, P = 0.000 9) and MDA (MD = -1.27, 95%CI was -1.57 to -0.96, P < 0.000 01) were significantly lowered. The overall effect value of the parameters with high heterogeneity was not significantly changed after furtherMeta-analysis excluding any one of the studies, suggesting that the result was relatively stable. Funnel chart analysis was used to analyze the parameters from more than 10 articles enrolled, and it showed that there was publication bias.@*Conclusion@#Xuebijing injection can reduce the mortality of patients with APP, which may because that it can improve liver and kidney function, reduce inflammation and oxidative stress damage, inhibit pulmonary fibrosis and increase oxygenation level.
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To explore the therapeutic effect of Xuebijing on patients with acute paraquat poisoning (APP) by using systematic evaluation method. Methods PubMed, Cochrane Library, Embase, Wanfang database, China National Knowledge Infrastructure (CNKI), VIP database (VIP) and China Biology Medicine (CBM) were searched using the computers to find the literatures published about the Xuebijing injection for the treatment of APP. Randomized controlled trials (RCT) were retrieved from the establishment of the database to August 2019. Patients in experimental group were treated with Xuebijing injection combined with conventional treatment, while the patients in control group were only given conventional treatment. The patients' outcome included the 14-day mortality, arterial oxygen saturation (SaO2) and incidence of pulmonary fibrosis. In addition, the 6-month survival rate, alanine aminotransferase (ALT), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups were compared. The literature data were extracted by two researchers independently, and the quality of the literatures was evaluated according to the Cochrane 5.1 handbook. The Meta-analysis was performed by using RevMan 5.3 software. The results stability of Meta-analysis was tested by sensitivity analysis. The publication bias was analyzed through drawing of funnel diagram. Results Twenty-seven RCT studies in total were enrolled, of which 26 were in Chinese and 1 was in English. A total of 1 429 patients were enrolled, among whom 726 were in experimental group and another 703 were in control group. Meta-analysis showed that compared with the control group, the 14-day mortality [relative risk (RR) = 0.62, 95% confidence interval (95%CI) was 0.54 to 0.72, P < 0.000 01] and incidence of pulmonary fibrosis (RR = 0.67, 95%CI was 0.53 to 0.85, P = 0.000 9) of patients in the experimental group were significantly lowered, while SaO2 at 7 days and 14 days were significantly increased [7 days:mean difference (MD) = 16.86, 95%CI was 9.89 to 23.83, P < 0.000 01; 14 days: MD = 16.51, 95%CI was 10.22 to 22.80, P < 0.000 01]. Compared with the control group, the survival rate within 6 months (RR = 1.55, 95%CI was 1.41 to 1.71, P < 0.000 01) and SOD (MD = 13.88, 95%CI was 7.43 to 20.33, P < 0.000 1) of patients in the experimental group were significantly increased, ALT at 14 days (MD = -78.35, 95%CI was -127.35 to -29.34, P = 0.000 5), SCr at 7 days and 14 days (7 days: MD = -135.13, 95%CI was -219.09 to -51.17, P = 0.002; 14 days: MD = -206.05, 95%CI = -290.13 to -121.96, P < 0.000 01), CRP (MD = -11.55, 95%CI was -17.77 to -5.33, P = 0.000 3), TNF-α (MD = -9.27, 95%CI was -15.48 to -3.96, P = 0.000 9) and MDA (MD = -1.27, 95%CI was -1.57 to -0.96, P < 0.000 01) were significantly lowered. The overall effect value of the parameters with high heterogeneity was not significantly changed after further Meta-analysis excluding any one of the studies, suggesting that the result was relatively stable. Funnel chart analysis was used to analyze the parameters from more than 10 articles enrolled, and it showed that there was publication bias. Conclusion Xuebijing injection can reduce the mortality of patients with APP, which may because that it can improve liver and kidney function, reduce inflammation and oxidative stress damage, inhibit pulmonary fibrosis and increase oxygenation level.