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Objective:To investigate the efficacy and safety of sivelestat sodium in patients with sepsis.Methods:The clinical data of 141 adult patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to January 1, 2022 were retrospectively analyzed. The patients were divided into the sivelestat sodium group ( n = 70) and the control group ( n = 71) according to whether they received sivelestat sodium or not. The efficacy indexes included oxygenation index, procalcitonin (PCT), C-reactive protein (CRP), white blood count (WBC), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) before and after 7 days of treatment, as well as ventilator supporting time, the length of ICU stay, the length of hospital stay and ICU mortality. The safety indicators included platelet count (PLT) and liver and kidney function. Results:There were no significant differences in age, gender, underlying diseases, infection site, basic drugs, etiology, oxygenation index, biochemical indexes, SOFA and APACHE Ⅱ scores between the two groups. Compared with the control group, the oxygenation index in 7 days was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 233.5 (181.0, 278.0) vs. 202.0 (153.0, 243.0), P < 0.01], the levels of PCT, CRP, alanine aminotransferase (ALT) and APACHE Ⅱ score were significantly decreased in the sivelestat sodium group [PCT (μg/L): 0.87 (0.41, 1.61) vs. 1.53 (0.56, 5.33), CRP (mg/L): 64.12 (19.61, 150.86) vs. 107.20 (50.30, 173.00), ALT (U/L): 25.0 (15.0, 43.0) vs. 31.0 (20.0, 65.0), APACHE Ⅱ: 14 (11, 18) vs. 16 (13, 21), all P < 0.05]. However, there were no significant differences in SOFA, WBC, serum creatinine (SCr), PLT, total bilirubin (TBil), aspartate aminotransferase (AST) in 7 days between the sivelestat sodium group and the control group [SOFA: 6.5 (5.0, 10.0) vs. 7.0 (5.0, 10.0), WBC (×10 9/L): 10.5 (8.2, 14.7) vs. 10.5 (7.2, 15.2), SCr (μmol/L): 76.0 (50.0, 124.1) vs. 84.0 (59.0, 129.0), PLT (×10 9/L): 127.5 (59.8, 212.3) vs. 121.0 (55.0, 211.0), TBil (μmol/L): 16.8 (10.0, 32.1) vs. 16.6 (8.4, 26.9), AST (U/L): 31.5 (22.0, 62.3) vs. 37.0 (24.0, 63.0), all P > 0.05]. The ventilator supporting time and the length of ICU stay in the sivelestat sodium group were significantly shorter than those in control group [ventilator supporting time (hours): 147.50 (86.83, 220.00) vs. 182.00 (100.00, 360.00), the length of ICU stay (days): 12.5 (9.0, 18.3) vs. 16.0 (11.0, 23.0), both P < 0.05]. However, there were no significant differences in the length of hospital stay and ICU mortality between the sivelestat sodium group and the control group [the length of hospital stay (days): 20.0 (11.0, 27.3) vs. 13.0 (11.0, 21.0), ICU mortality: 17.1% (12/70) vs. 14.1% (10/71), both P > 0.05]. Conclusions:Sivelestat sodium is safe and effective in patients with sepsis. It can improve the oxygenation index and APACHE Ⅱ score, reduce the levels of PCT and CRP, shorten ventilator supporting time and the length of ICU stay. No adverse reactions such as liver and kidney function injury and platelet abnormality are observed.
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OBJECTIVE@#To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites.@*METHODS@#A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis.@*RESULTS@#At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities.@*CONCLUSIONS@#Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.
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Ratos , Masculino , Animais , Ratos Sprague-Dawley , Microbioma Gastrointestinal , RNA Ribossômico 16S , Sepse/metabolismo , InflamaçãoRESUMO
Objective:To explore the relationship between the changes in the lipid profiles and the intensity of inflammatory response and disease severity in patients with sepsis, in order to find a biomarker that can quickly evaluate the condition and prognosis of sepsis.Methods:A retrospective analysis was performed on 449 patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from October 2019 to May 2021, and 355 patients without sepsis hospitalized in the same period served as the control. The general demographic data, blood lipid and other clinical indicators within 24 hours after admission were collected and compared between the two groups. Bivariate correlation study was used to analyze the relationship between blood lipid levels and inflammation indicators and severity of illness in patients with sepsis. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each blood lipid component on the 28-day mortality of patients with sepsis. According to the results of ROC curve analysis, the blood lipids were divided into two groups with different levels, and the Kaplan-Meier survival curve was used to compare the cumulative survival rates of the two groups without end-point event (the 28-day mortality was the end-point event).Results:Compared with non-septic patients, the levels of plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were significantly lower in patients with sepsis [TC (mmol/L): 2.93±1.33 vs. 4.01±1.14, HDL-C (mmol/L): 0.78±0.47 vs. 1.16±0.40, LDL-C (mmol/L): 1.53±1.00 vs. 2.71±0.98, all P < 0.05]. In patients with sepsis, plasma cholesterol levels were correlated with the degree of inflammation and severity of the disease to varying degrees, but the HDL-C had the strongest correlation with interleukin-6 (IL-6; r = -0.551, P = 0.000), procalcitonin (PCT, r = -0.598, P = 0.000), sequential organ failure assessment (SOFA; r = -0.285, P = 0.000). The ROC curve analysis showed that among all blood lipid components, HDL-C had the highest predictive value for 28-day mortality of sepsis patients, and the area under the ROC curve (AUC) was 0.718, when the best cut-off value was 0.69 mmol/L, the sensitivity and specificity were 67.3% and 65.2% respectively, and the positive predictive value and negative predictive value were 60.6% and 71.5% respectively. According to Kaplan-Meier survival curve analysis, the mortality of sepsis patients with HDL-C ≤ 0.69 mmol/L was significantly higher than the patients with HDL-C > 0.69 mmol/L, and the difference was statistically significant ( P < 0.000 1). In addition, the 28-day mortality [59.73% (135/226) vs. 28.70% (64/223)], the incidence of multiple organ dysfunction [41.15% (93/226) vs. 31.84% (71/223)], the probability of requiring mechanical ventilation and vasoactive drugs [mechanical ventilation: 56.64% (128/226) vs. 46.18% (103/223); vasoactive drugs: 54.42% (123/226) vs. 38.57% (86/223)], the positive rate of microbial culture [45.58% (103/226) vs. 35.43% (79/223)], and the probability of drug-resistant bacteria [19.91% (45/226) vs. 10.31% (23/223)] in the low HDL-C group of sepsis patients were all higher than the high HDL-C group, the differences were statistically significant (all P < 0.05). Conclusions:Plasma cholesterol levels, especially the HDL-C levels, can well reflect the intensity of inflammation and the severity of the disease in patients with sepsis. And the HDL-C levels can be used as a good biomarker for predicting the short-term prognosis of sepsis.
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Objective:To investigate the changes of intestinal microecology in the early stage of sepsis rat model by 16S rDNA sequencing.Methods:Sixty male Sprague-Dawley (SD) rats were randomly divided into cecal ligation and puncture (CLP) group and sham operation group (Sham group), with 30 rats in each group. In the CLP group, sepsis rat model was reproduced by CLP method; the rats in the Sham group only underwent laparotomy without CLP. At 24 hours after the operation, the intestinal feces and serum samples of 8 rats in each group were collected. The survival rate of the rest rats was observed until the 7th day. The level of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Intestinal feces were sequenced by 16S rDNA sequencing technology. The operational taxonomic unit (OTU) data obtained after sequence comparison and clustering was used for α diversity and β diversity analysis, principal coordinate analysis and linear discriminant analysis effect size analysis (LEfSe) to observe the changes of intestinal microecology in early sepsis rats and excavate the marker flora.Results:At 24 hours after the reproduction of the model, the rats in the CLP group showed shortness of breath, scattered hair and other manifestations, and the level of serum TNF-α increased significantly as compared with that in the Sham group (ng/L: 43.95±9.05 vs. 11.08±3.27, P < 0.01). On the 7th day after modeling, the cumulative survival rate of the Sham group was 100%, while that of the CLP group was 31.82%. Diversity analysis showed that there was no significant difference in α diversity parameter between the Sham group and the CLP group (number of species: 520.00±52.15 vs. 492.25±86.61, Chao1 richness estimator: 707.25±65.69 vs. 668.93±96.50, Shannon index: 5.74±0.42 vs. 5.79±0.91, Simpson index: 0.93±0.03 vs. 0.94±0.05, all P > 0.05). However, the β diversity analysis showed that the difference between groups was greater than that within groups whether weighted according to OTU or not (abundance weighted matrix: R = 0.23, P = 0.04; abundance unweighted matrix: R = 0.32, P = 0.01). At the phylum level, the abundance of Proteobacteria and Candidatus_sacchari in the CLP group increased significantly as compared with the Sham group [18.100% (15.271%, 26.665%) vs. 6.974% (2.854%, 9.764%), 0.125% (0.027%, 0.159%)% vs. 0.018% (0.008%, 0.021%), both P < 0.05]. At the genus level, the abundance of opportunistic pathogen including Helicobacter, Ruthenium, Streptococcus, Clostridium ⅩⅧ in the CLP group was significantly higher than that in the Sham group [5.090% (1.812%, 6.598%) vs. 0.083% (0.034%, 0.198%), 0.244% (0.116%, 0.330%) vs. 0.016% (0.008%, 0.029%), 0.006% (0.003%, 0.010%) vs. 0.001% (0%, 0.003%), 0.094% (0.035%, 0.430%) vs. 0.007% (0.003%, 0.030%), all P < 0.05], and the abundance of probiotics such as Alloprevotella and Romboustia was significantly lower than that in the Sham group [7.345% (3.662%, 11.546%) vs. 22.504% (14.403%, 26.928%), 0.113% (0.047%, 0.196%) vs. 1.229% (0.809%, 2.29%), both P < 0.01]. LEfSe analysis showed that the probiotics belonging to Firmicutes were significantly enriched in the Sham group, and Romboustia was the most significantly enriched species. Opportunistic pathogens such as Helicobacter, Streptococcus and Clostridium ⅩⅧ were significantly enriched in the CLP group, Helicobacter_NGSU_ 2015 was the most significantly enriched species. Conclusion:In the early stage of sepsis, the intestinal microbiota structure of rats is significantly changed, which mainly shows that the abundance of Alloprevotella and other probiotics is significantly reduced, while that of Helicobacter and other opportunistic pathogens is significantly increased.
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Objectve:To study the effect of gabexate mesylate (GM) on acute lung injury (ALI) in septic rats based on metabonomics.Methods:Fifty-seven SD rats were randomly(random number) divided into three groups: sham operation group (SC group), cecal ligation puncture induced septic ALI group (CLP group), and intraperitoneal administration of GM at 1 h after CLP (CLP-GM group). Twenty-four h after the experiment, the survival of rats in the SC, CLP and CLP-GM groups was observed, the lung tissue was collected for HE staining to observe the pathological changes, and the plasma was collected for metabonomics detection to analyze the characteristics of metabolites.Results:Compared with the SC group, the infiltration of inflammatory cells in the lung tissue of rats in the CLP groupincreased significantly, and the metabolic profile of plasma changed significantly. However, the pathological and metabonomic characteristics of the CLP-GM group showed that the above changes were reversed after the application of GM. Twelve major differential metabolites were found in plasma. The metabolic pathways involved in the disorder included biosynthesis of phenylalanine, tyrosine and tryptophan, phenylalanine metabolism and sphingolipid metabolism.Conclusions:GM may improve septic ALI by regulating amino acid metabolism, sphingolipid metabolism and other metabolic pathways.
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Objective:To investigate the role of KLF4 in lipopolysaccharide induced cardiomyocyte injury.Methods:Primary rat cardiomyocytes were isolated and cultured, and randomly divided into 5 groups: control group, negative control (NC), LPS group, KLF4 overexpression group, KLF4 overexpression+LPS group. MTT method was used to detect cell activity, ROS, SOD 2, GPX and MDA were detected by kit, TNFa, IL-1 β and IL-6 were detected by ELISA. TUNEL staining was used to detect apoptosis. The protein levels of TLR4 and Nrf2 were detected by Western blot.Results:The expression of KLF4 in cardiomyocytes was significantly higher than that in the NC group ( P<0.001). The cell activity of LPS group was significantly lower than that of NC group ( P < 0.001), and that of KLF4 overexpression +LPS group was higher than that of LPS group ( P<0.001). The levels of TNFa, IL-1 β and IL-6 in LPS group were significantly higher than those in the NC group ( P<0.0001), and the levels of TNFa, IL-1 β and IL-6 in KLF4 overexpression +LPS group were lower than those in LPS group ( P<0.0001). The levels of ROS and MDA in LPS group were significantly higher than those in the control group, while the activities of SOD2 and GPX were lower than those in the NC group ( P<0.0001); the levels of ROS and MDA in KLF4 overexpression +LPS group were lower than those in LPS group, while the activities of SOD2 and GPX were higher than those in LPS group ( P<0.0001). The number of apoptosis in LPS group was significantly higher than that in the NC group, and that in KLF4 overexpression +LPS group was lower than that in LPS group ( P< 0.001). The level of TLR4 wan higher and Nrf2 protein in the nucleus of LPS group was lower than that of the NC group. The level of TLR4 was lower and Nrf2 protein in the nucleus of KLF4 overexpression+LPS group was significantly higher than that of LPS group ( P < 0.001). Conclusions:KLF4 can alleviate LPS induced cardiomyocyte injury by regulating TLR4 and NRF2 signals.
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Objective:To investigate the clinical treatment and assess the knowledge and use of the coronavirus disease 2019 (COVID-19) treatment plan issued by the nation.Methods:A nationwide questionnaire survey on line was administered to medical staffs involved in COVID-19 treatment on February 28th, 2020. The questionnaire included drug treatment, respiratory support therapy, sedation and analgesia, continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), etc.Results:There were 1 103 respondents, of whom 699 (504 doctors and 195 nurses) participated in the treatment of COVID-19. Finally, 432 doctors and 170 nurses from 9 provinces submitted valid questionnaires. The results of the questionnaire surveys of doctors and nurses were basically the same. Considering that doctors dominated in the diagnosis and treatment of COVID-19, the results of the questionnaires of doctors were mainly analyzed. The doctors participating in the survey were mainly from Hubei (29.2%), followed by Henan (24.5%), Guizhou (22.7%), and Guangxi (14.6%), etc. 55.4% of the doctors came from tertiary three hospitals, and most of them have senior titles (56.4%). 232 doctors (53.7%) participated in the treatment of mild COVID-19, and 200 doctors (46.3%) participated in the treatment of severe and critically ill patients. More than 95% of the doctors expressed that they would carry out antiviral treatment for patients with COVID-19 regardless of disease severity. The main antiviral drugs included α-interferon (69.5%), lopinavir/ritonavir (65.0%), abidol (60.0%), and ribavirin (55.7%). The choice of antiviral drugs was highly consistent with the national treatment programs of COVID-19. At the same time, 95.5% of doctors would routinely prescribe antibiotics to severe and critically ill patients. 94.0% of doctors agreed to prescribe low-dose glucocorticoid therapy to severe and critically ill patients. About 2/3 of doctors would perform lung recruitment or prone position treatment for critical patients with invasive ventilation. 79.0% of doctors preferred to use deep sedation for patients with invasive ventilation. About 1/3 of doctors believed that CRRT should be initiated early, and nearly 1/3 of doctors suggested that ECMO should be used more aggressively in critically ill patients.Conclusions:Medical staffs are familiar with the national treatment plan of COVID-19 and willing to follow it. However, as a new disease, we have limited knowledge about COVID-19 and there are still many controversies. Further practical training is needed to make clinicians more aware of the disease, and more evidence-based evidence is needed to guide clinical treatment.
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Objective:To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS).Methods:A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels.Results:A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHEⅡ score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk ( RR) = 1.444, 95% confidence interval (95% CI) was 1.090-1.914, P = 0.010], APACHEⅡ score ( RR = 2.249, 95% CI was 1.688-2.997, P = 0.000), SChE ( RR = 1.469, 95% CI was 1.057-2.043, P = 0.022), and Lac ( RR = 2.190, 95% CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHEⅡ score and Lac was greater than APACHEⅡ score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group ( n = 88), the 28-day mortality of patients in the low SChE group ( n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ 2 = 5.852, P = 0.016). Conclusions:Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.
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Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.
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Objective To evaluate the effectiveness of a comprehensive hypertension management. Methods Hypertensive patients aged≥35 years in the Zhengfei community of Zhengzhou were selected. The patients were randomly assigned to the intervention and control groups. Those in intervention group received comprehensive hypertension management from October 2015 to September 2016,whereas those in the control group received the original management mode. Scales to assess blood pressure control, biochemical indexes, unhealthy lifestyle, and cardiovascular disease associated risk level were used to evaluate the effectiveness of the management modes.Results Each study groups had 1 051 patients.There were no significant differences in the baseline data of the two groups (P>0.05). At the end of 1 year of receiving the respective hypertension management modes, each group had 941 patients. Findings revealed that after receiving the comprehensive hypertension management mode, the systolic and diastolic blood pressure in the intervention group decreased by(9.87±7.38)mmHg(1 mmHg=0.133 kPa)and(6.33±4.14) mmHg,respectively.Those in the control group decreased by(7.01±6.02)mmHg and(4.52±3.59)mmHg, respectively,statistically significant differences in the extent of reduction of blood pressure between the two groups (P<0.05). Further, the fasting plasma glucose, postprandial blood glucose, low density lipoprotein, serum creatinine,and microalbuminuria levels in the intervention group were significantly lower than those in the control group(all P<0.05).However,the intervention group exhibited a significant increase in the high density lipoprotein level as compared to the control group(P<0.05).There were no significant differences in the total cholesterol,triglyceride,urinary creatinine levels,and body mass index between the two groups(P>0.05), although they had decreased in both groups. After the 1-year management, these proportions of smoking,heavy drinking,high salt diet and need to exercise were 10.0%,3.7%,20.1%,and 48.9% in the intervention group, and 15.3%, 10.0%, 29.0%, and 54.3% in the control group. The proportions were significantly different between the two groups (P<0.05). After the 1-year management, these proportions of low,moderate,and high risk of cardiovascular disease were 13.3%,33.5%,and 53.2% in the intervention group, and 11.2%, 30.1%, and 58.8% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). After the 1-year management, the proportion of treated, controlled, and control-treated hypertension using medication was 100%, 65.1%, and 75.3% in the intervention group, and 39.5%, 60.3%, and 70.0% in the control group, respectively, with statistically significant differences between the two groups (P< 0.05). Conclusion The comprehensive hypertension management mode was effective in significantly improving the blood pressure and health condition of hypertensive patients.
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Objective To test the reliability and validity of the Chinese Version of the Student Nurse Stress Index Scale ( SNSI-CHI ) among Chinese nursing students. Methods A random sampling method was used to collect 1100 nursing students who were from two medical universities of Henan Province, China,and SPSS 17. 0 and AMOS 17. 0 software were used. Results The average total score of SNSI-CHI was 58. 46±13. 90. The Cronbach's α was 0. 886,the test-retest intra-class correlation coefficient( ICC) of SNSI-CHI was 0. 996 (95％CI:0. 992-1. 000,P<0. 01). The item-to-total correlations ranged from 0. 351 to 0. 664 ( all P<0. 01) . The content validity index( CVI) was 0. 954. The result of exploratory factor analysis ( EFA) was that three factors together explained 75. 013％ of the total variances,and the confirmatory factory analysis( CFA) also indicated a good fit (χ2/df=1. 347,GFI=0. 956,AGFI=0. 945,RMR=0. 032,RMSEA= 0. 025, NFI=0. 974, IFI=0. 993, TLI=0. 992, CFI=0. 993 ) . Criterion-related validity was between 0. 330 and 0. 903 ( all P<0. 01) . Conclusion The SNSI-CHI is proved to be reliable and valid in China, and it can be used to measure the stress of Chinese nursing students.
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Objective To test the agreement between two new self-care-related instruments,the Chinese version of the Appraisal of Self-care Agency Scale-Revised (ASAS-R-CHI) and the Chinese version of the Self-care Ability Scale for the Elderly (SASE-CHI) among older stroke patients by Bland-Altman method.Methods A random sampling was used to conduct this study in Neurology Department in a tertiary referral hospital in Henan Province,during November 2016 to October 2017.The sample consisted of 500 older stroke patients.Data were collected by a demographic questionnaire,SASE-CHI and ASAS-R-CHI.SPSS 21.0 was used to analyze the data.Results The mean total scores of ASAS-R-CHI and SASE-CHI were 54.98±5.06 and 61.92±7.34,respectively.Partial correlation coefficients between the total score of ASAS-R-CHI and SASE-CHI and their factors were from 0.217 to 0.953,showed significantly correlation (P＜0.01).The difference analysis and ratio analysis of Bland-Altman showed a good consistency of the two scales,with 5.0％ and 4.5％ of the points outside the 95％CI boundaries,separately.Conclusion There is a good agreement between the two instruments among older stroke patients.Each scale has its own characteristics,therefore the users should choose the most appropriate scale according to the specific situation.
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Objective:To systematically review the efficacy and safety of dexmedetomidine and midazolam in procedural sedation. Methods: PubMed,EMBase,Cochrane Library,CNKI,CBM and WanFang databases were retrieved to collect the randomized controlled trials (RCT) about comparion of efficacy and safety between dexmedetomidine and midazolam in procedural sedation up to March, 2017. Based on the inclusion criteria, the data extraction and quality evaluation were performed, and then the systematic evaluation was carried out.The outcome measures for efficacy were the satisfaction scores and pain scores of the patients and clinicians;the outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications.Results:There were 14 RCT satisfied the inclusion criteria including 949 patients.Compared with midazolam group, the incidence of pain, delirium, and analgesia of the patients in dexmedetomidine group had significant differences (P0.05).Conclusion:When the adult patients are sedated, dexmedetomidine can be used as an ideal alternative to midazolam sedation.
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Objective:To investigate the effects of hematopoietic progenitor kinase 1 (HPK1) overexpression by construction of lentiviral vector on the proliferation and apoptosis of breast cancer MCF-7 and MDA-MB-231 cells,and to elucidate its possible mechanism.Methods:The cells were infected with the lentivirus overxpressing HPK1,and the MCF-7-HPK1 and MDA-MB-231-HPK1 cell lines were stably expressed HPK1;each cell line was divided into three experimental groups:blank group (untreated),control group (empty vector) and HPK1-overexpression group.The expression levels of HPK1 mRNA and protein in breast cancer cells in each group were detected by RTPCR and Western blotting methods,respectively.The cell proliferation rate was detected by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry.Transwell assay was used to analyze the cell migration ability.Western blotting method was used to measure the expression levels of caspase 3,PTEN,MMP-9,MMP-2,Ki-67and HPK1 proteins.Results:Compared with blank groups and control groups,the expression levels of HPK1 mRNA and protein in the both cell lines in HPK1 overexpression groups were significantly up-regulated (P＜0.05),the proliferation rates were significantly decreased (P＜0.05) and the apoptotic rates were significantly increased (P＜0.05),the number of cells crossing matrigel was significantly reduced (P＜0.05),the cell cycle of MCF-7 was blocked in G1 phase (P＜0.05),the expression levels of caspase 3 and PTEN proteins in HPK1 overexpression group were significantly increased (P＜0.05),and the expression levels of MMP-2 and MMP-9 proteins were significantly decreased (P＜0.05).Conclusion:HPK1 overexpression can inhibit the proliferation and migration of MCF-7 and MDA-MB-231 cells and induce apoptosis,which may be related to the up-regulation of caspase 3 and PTEN and down-regulation of MMP-9,MMP-2 and Ki-67.
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Objective:To investigate the effects of hematopoietic progenitor kinase 1 (HPK1) overexpression by construction of lentiviral vector on the proliferation and apoptosis of breast cancer MCF-7 and MDA-MB-231 cells,and to elucidate its possible mechanism.Methods:The cells were infected with the lentivirus overxpressing HPK1,and the MCF-7-HPK1 and MDA-MB-231-HPK1 cell lines were stably expressed HPK1;each cell line was divided into three experimental groups:blank group (untreated),control group (empty vector) and HPK1-overexpression group.The expression levels of HPK1 mRNA and protein in breast cancer cells in each group were detected by RTPCR and Western blotting methods,respectively.The cell proliferation rate was detected by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry.Transwell assay was used to analyze the cell migration ability.Western blotting method was used to measure the expression levels of caspase 3,PTEN,MMP-9,MMP-2,Ki-67and HPK1 proteins.Results:Compared with blank groups and control groups,the expression levels of HPK1 mRNA and protein in the both cell lines in HPK1 overexpression groups were significantly up-regulated (P＜0.05),the proliferation rates were significantly decreased (P＜0.05) and the apoptotic rates were significantly increased (P＜0.05),the number of cells crossing matrigel was significantly reduced (P＜0.05),the cell cycle of MCF-7 was blocked in G1 phase (P＜0.05),the expression levels of caspase 3 and PTEN proteins in HPK1 overexpression group were significantly increased (P＜0.05),and the expression levels of MMP-2 and MMP-9 proteins were significantly decreased (P＜0.05).Conclusion:HPK1 overexpression can inhibit the proliferation and migration of MCF-7 and MDA-MB-231 cells and induce apoptosis,which may be related to the up-regulation of caspase 3 and PTEN and down-regulation of MMP-9,MMP-2 and Ki-67.
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Objective: To investigate the inhibitory effect of metformin on the proliferation of esophageal cancer KYSE450 cells, and to explore its possible mechanism. Methods: The human esophageal cancer KYSE450 cells were cultured in vitro and treated with different concentrations of metformin (5, 10, 20 and 40 mmol/L). The proliferation and apoptosis of KYSE450 cells after metformin treatment were detected by MTT and FCM method, respectively. The expression levels of 4E-binding protein 1 (4EBP1) and S6 kinase 1 (S6K1) mRNAs and proteins were detected by semi-quantitative RT-PCR and Western blotting, respectively. The subcutaneous tumor xenograft models of esophageal squamous cell carcinoma KYSE450 cells in nude mice were constructed, and were divided into two groups at the 7th day after injection with KYSE450 cells. In the two groups, metformin or 0.9% sodium chloride solution was separately used by intraperitoneal injection for 15 d. The size of tumor was measured every 3 days. The cell morphological characteristics of tumor xenografts were detected by HE staining. The expressions of S6K1 and 4EBP1 proteins in xenograft tumor tissues were detected by immunohistochemistry. Results: Different concentrations of metformin (5, 10, 20 and 40 mmol/L) could obviously inhibit the proliferation of KYSE450 cells in a dose- and time-dependent manner (all P<0.0001). The apoptosis rates of KYSE450 cells treated with 5, 10 and 20 mmol/L metformin were increased in a concentration-dependent manner (all P<0.05). The expression levels of 4EBP1 and S6K1, two downstream molecules of mammalian target of rapamycin (mTOR), in KYSE450 cells were significantly down-regulated with the increasing of concentrations or time of metformin treatment (all P<0.05). The growth of tumor xenografts in nude mice of metformin group was significantly suppressed (P < 0.0001). The expression levels of 4EBP1 and S6K1 proteins in tumor xenograft tissues were significantly down-regulated after metformin injection (both P<0.05). Conclusion: Metformin can inhibit the proliferation of esophageal cancer KYSE450 cells in vitro and in vivo, and its mechanism may be related to the down-regulation of 4EBP1 and S6K1 expressions in the downstream pathway of mTOR.
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Objective To explore the effect of adipose-derived stem cells (ADSCs) on inflammatory factors in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the possible mechanism of anti-inflammatory. Methods Seventy male Sprague-Dawley (SD) rats were randomly divided into normal control group (n = 10), LPS model group (n = 30), and ADSCs intervention group (n = 30) by random number table. ALI model was reproduced by intraperitoneal injection of 8 mg/kg LPS, and the rats in ADSCs intervention group received tail vein injection of 300 μL ADSCs 30 minutes after the model reproduction, the samples of normal control group were harvested immediately without any intervention, and the specimens in remained two groups were taken at 6, 24, 72 hours respectively. Arterial partial pressure of oxygen (PaO2) and lactate level in femoral artery were determined. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum myeloperoxidase (MPO) and interleukin-10 (IL-10) in the blood of left ventricle. Lung wet/dry weight (W/D) ratio was detected by thoracotomy, and the pathological changes of lung tissue were observed under an optical microscope. Western Blot was used to detect the protein expression of nuclear factor-κB (NF-κB) in lung tissue of rats. Results Compared with the normal control group, the damage degree of lung tissue of LPS model group was significantly heavier from 6 hours, and lung W/D ratio, blood lactate, MPO, IL-10 and expression level of NF-κB in lung tissue were significantly increased respectively, while PaO2 was decreased significantly. Compared with LPS model group, the damage degree of lung tissue of ADSCs intervention group was significantly reduced from 6 hours, and lung W/D ratio, blood lactate, MPO, and NF-κB expression in lung tissue were significantly decreased, while PaO2 was increased significantly, and it became normal at 72 hours [lung W/D ratio: 5.33±0.29 vs. 5.77±0.42 at 6 hours, 5.14±0.46 vs. 5.43±0.38 at 72 hours; blood lactate (mmol/L): 3.6±1.0 vs. 5.7±1.1 at 6 hours, 3.1±1.0 vs. 3.8±1.2 at 72 hours; blood MPO (μg/L): 1.50±0.90 vs. 2.70±1.85 at 6 hours, 0.46±0.30 vs. 0.71±0.22 at 72 hours; NF-κB (gray value): 0.40±0.11 vs. 0.50±0.09 at 6 hours, 0.24±0.03 vs. 0.33±0.06; PaO2 (mmHg, 1 mmHg = 0.133 kPa): 78.0±4.1 vs. 74.5±3.2 at 6 hours, 89.3±9.4 vs. 81.9±3.4 at 72 hours; all P < 0.05]. The IL-10 level was significantly higher than that of LPS model group only at 24 hours (ng/L: 27.75±15.49 vs. 17.52±6.56, P < 0.05). Conclusion ADSCs can effectively relieve the inflammatory response of ALI induced by LPS, probably by inhibiting the expressions of NF-κB and blocking the release of inflammatory cytokines.
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Objective:To explore the expression of mammalian target of rapamycin (mTOR)and its relationgship with the prognosis of breast cancer,and to provide evidence-based basis for the using of mTOR inhibitor in the treatment of breast cancer.Methods: A systemical literature search was conducted based on the following databases:PubMed,EMBbase,Cochrane Library,ISI Web of Science,and CNKI up to November 24,2015.The outcome measures were hazard ratio (HR)with 95% confidence interval (CI) for the association between the mTOR expression and the prognosis of patients with breast cancer.The primary end points including disease-free survival (DFS ), and overall survival (OS ). STATA 12.0 was used to conduct the statistical analysis. Results:A total of seven cohort studies,1 758 patients were included. The risk of recurrence and metastasis of the breast cancer patients with positive expression of mTOR was 2.05 times of the patients with negative expression of mTOR (HR= 2.05, 95% CI: 1.01 - 4.13,P = 0.003);the risk of death in the breast cancer patients with positive expression of mTOR was 2.63 times of the patients with negative expression of mTOR (HR = 2.63, 95%CI:1.45-4.80,P = 0.736).Conclusion:The positive expression of mTOR can significantly increase the recurrence,metastasis and death risk of the patients with breast cancer.