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Objective:To investigate the mechanism of dexmetomidine (DEX) in improving lung injury in septic mice.Methods:Male C57BL/6 mice were randomly assigned to the blank group (NC), sham operation group (sham), cecal ligation and puncture group (CLP), and Dex treatment group (CLP+DEX), 36 mice per group. Mice in the CLP group were intraperitoneally injected with 1 mL sterile saline 15 min before CLP, and mice in the CLP + DEX group were intraperitoneally injected with 50 μg/kg DEX 15 min before CLP. The survival rate was recorded within 24 h after CLP. The mice were sacrificed at 0, 3, 6, 12, and 24 h after CLP, and lung tissues were collected. The expression levels of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in the lung of mice were detected by qPCR. RAW264.7 cell were cultured in vitro, LPS (100 ng/mL) and DEX (1 μ mol/L) were used to establish a cell model for studying the mechanism of Dex, and the expression of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in RAW264.7 cell model were detected by qPCR. In addition, the effect of lncRNA-HOTAIR on sepsis was explored in vivo and in vitro by knockdown or overexpression of HOTAIR.Results:The survival rate of the CLP+DEX group was higher than that of the CLP group within 24 h after surgery, and the levels of IL-6, IL-1β, and TNF-α in the lungs were significantly lower than those in the CLP group at 6, 12, and 24 h after surgery ( P<0.05). In addition, the level of lncRNA HOTAIR showed that the expression level of lncRNA HOTAIR in the lungs of mice were decreased after Dex treatment, and were decreased 1.1 times ( P<0.05), 4.0 times ( P<0.01) and 3.8 times ( P<0.01) at 6, 12, and 24 h, respectively. Compared with the NC group, knockdown of HOTAIR significantly decreased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.05), and overexpression of HOTAIR significantly increased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.01). Conclusions:DEX can reduce the production of inflammatory factors in the lungs of septic mice and improve the survival rate of septic mice. The mechanism may be related to the inhibition of HOTAIR expression.
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Delirium is a common and serious multifactorial syndrome in elderly inpatients and may have serious consequences for patients, their families and society.This review summarizes the epidemiology, risk factors, pathogenesis, evaluation criteria, prevention and treatment of delirium in elderly inpatients.
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Objective:To investigate the protective effect and mechanism of hydroxysafflor yellow A (HSYA) on severe acute pancreatitis (SAP) related lung injury.Methods:Fifty mice were randomly (random number) divided into five groups: the sham-operated group, SAP group and different doses (20, 40 and 80 mg/kg) of HSYA pretreatment group. Mice were pretreated with HSYA 24 h before SAP induction, pancreatic and lung tissues were isolated for histopathological examination at 72 h after modeling, and bronchoalveolar lavage fluid (BALF) was collected for biochemical analysis. Results:Compared with the sham-operated group, serum amylase activity, lung injury pathological score and BALF protein concentration in the SAP group were significantly increased [(2120.44 ± 354.50) U/L vs. (226.72 ± 20.84) U/L; (6.91 ± 0.28) vs. (0.53±0.18); (2563.25±348.22) μg/mL vs. (345.62±56.35) μg/mL, all P<0.05]. Inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels and myeloperoxidase (MPO) activity were increased [(120.5±14.25) pg/mL vs. (31.5±4.82) pg/mL; (214.72±10.62) pg/mL vs. (39.26±5.66) pg/mL; (4.52±0.34) U/mg vs. (1.03±0.17) U/mg]. Compared with the SAP group, HSYA pretreatment significantly attenuated SAP-related pancreatic and lung tissue damage and the activities of the inflammatory factors TNF-α, IL-6 and MPO in BALF. In addition, HSYA promoted the expression of the antioxidant protein heme oxygenase-1 and blocked the activation of the NF-κB signaling pathway. Conclusions:HSYA exerts anti-inflammatory and antioxidant activities to inhibit SAP-related lung injury, which indicated that HSYA may be a potential therapeutic drug for SAP-induced lung injury.
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Objective To investigate the research hotspots and trends in the field of immunotherapy for liver cancer in 2011-2020 based on bibliometric methods. Methods The Web of Science-SCI Expanded database was searched with the following search strategy: #1 TS = (Liver Neoplasms OR Neoplasms, Hepatic OR Neoplasms, Liver OR Liver Neoplasm OR Neoplasm, Liver OR Hepatic Neoplasms OR Hepatic Neoplasm OR Neoplasm, Hepatic OR Cancer of Liver OR Hepatocellular Cancer OR Cancers, Hepatocellular OR Hepatocellular Cancers OR Hepatic Cancer OR Cancer, Hepatic OR Cancers, Hepatic OR Hepatic Cancers OR Liver Cancer OR Cancer, Liver OR Cancers, Liver OR Liver Cancers OR Cancer of the Liver OR Cancer, Hepatocellular) AND #2 TS = (Immunotherapy OR Immunotherapies OR Immunity therapy); time span: 2011-2020; type of literature: Article; language: English. CiteSpace software was used to perform a visualized analysis of the articles in the field of immunotherapy for liver cancer published in 2011-2020 from the aspects of the distributions of year, country, institution, author, journal, and fund, times cited, and keywords, and the frequency, centrality, and clustering of keywords were discussed. Results A total of 1972 articles on immunotherapy for liver cancer were included, and the analysis showed that China was the country with the largest number of articles, Sun Yat-sen University was the institution with the largest number of articles, and Journal for Immunotherapy of Cancer was the journal with the largest number of articles. The research hotspots in this field included tumor-associated macrophages, oncolytic virus (such as adenovirus), tumor vaccine therapy, adoptive cellular immunotherapy, immune checkpoint inhibitors, and combined immunotherapy. The trend of this field was tumor vaccine therapy → immunotherapy for oncolytic virus → adoptive cellular immunotherapy → immune checkpoint inhibitor therapy. Conclusion Immunotherapy for liver cancer has undergone continuous development in the recent ten years, and with the research and development of tumor vaccine therapy, oncolytic virus, and immune checkpoint inhibitors and the improvement of immune checkpoint inhibitors, combined treatment based on immunotherapy is expected to further improve the clinical outcome of liver cancer.
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Objective To explore the research hotspots and trends in the field of CSCs through the bibliometric analysis of the literature on CSCs. Methods Based on the core database of Web of Science, CiteSpace was used to analyze the annual distribution of published articles, authors, institutions, countries, journals, citations and keywords, and to explore the frequency, centrality and clustering of key words. Results (1) A total of 8131 articles were included after screening. China was the country with the largest number of articles, and Sun Yat-Sen University was the organization with the largest number of articles; (2) The hot spots in the field of CSCs are the research of CSCs in breast cancer and pancreatic cancer, the research of CSCs sorting and identification of molecular markers ALDH and genes PTEN, Sox2, C-myc, EZH2, the mechanism of EMT inducing the production of CSCs and promoting tumor metastasis, cellular and molecular mechanisms of CSCs resistance to chemical, radiation and targeted drug attacks, Wnt/β-catenin signaling pathway and tumor microenvironment regulate the differentiation of CSCs and targeted inhibition of CSCs in the treatment of malignant tumors; (3) The research trend of CSCs is CSCs stem research-biological mechanism of CSCs-CSCs application in the treatment of cancer. Conclusion The focus and direction of CSCs research are EMT inducing CSCs to promote tumor metastasis, CSCs resisting chemical attack, mesenchymal stem cells regulating CSCs, the metabolism of CSCs, and inhibitors targeting CSCs at present and in the future.
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Objective:To evaluate the accuracy of serum concentration of procalcitonin (PCT) in differential diagnosis of the etiology of bloodstream infections (BSI).Methods:Patients hospitalized in ICU of China-Japan Friendship Hospital from January 2015 to June 2020 with BSI and with PCT test simultaneously when blood drawing for blood culture were enrolled. Sequential Organ Failure Assessment (SOFA) were calculated based on parameters on the day of blood culture. Difference of various indicators among different pathogen infections were compared. Receiver Operating Characteristic (ROC) Curve was used to analyze the value of PCT in differential diagnosis of BSI by different pathogens.Results:Among 1 456 patients with BSI,1 261 (86.6%) patients with monobacterial infection, 80 (5.5%) patients with candidiasis and 115 (7.9%) patients with mixed infection. The 28-day mortality was 24.5% (356/1 456) and the 60-day mortality was 30.6% (446/1456). Mortality of both 28-day and 60-day in the mixed group was significantly higher than that in the bacteriacemia group and candidemia group. PCT levels was significantly higher in patients with bacteremia caused by gram-negative bacteria (GNB) than that in gram-positive bacteria (GPB) infected bacteremia and candidemia {3.4 μg/L[95% confidence interval (95% CI) 0.7-17.0 μg/L] vs 1.3 μg/L (95% CI 0.4-7.3 μg/L); 3.4μg/L (95% CI was 0.7-17.0 μg/L) vs 1.1 μg/L (95% CI was 0.4-3.4 μg/L); P<0.01} . ROC curve analysis showed that: ① the optimal cut-off value of PCT in differential diagnosis of monobacterial bacteremia and candidemia was 7.25 μg/L, with specificity of 90.0% and the area under the ROC curve (AUROC) was 0.612 (95% CI 0.533-0.691). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia could reach 73.3%. ② the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB infection and candidemia was 7.32 μg/L, with specificity of 90.0% and AUROC was 0.695 (95% CI 0.614-0.776). When PCT value was greater than 0.51 μg/L, the sensitivity of diagnostic of bacteremia caused by GNB infection was 84.9%.③ the optimal cut-off value of PCT in differential diagnosis of bacteremia caused by GNB and GPB infection was 0.52 μg/L, with sensitivity of 84.9% and AUROC was 0.713 (95% CI 0.672-0.755). When PCT value was greater than 7.36 μg/L, the specificity of diagnostic of bacteremia caused by GNB infection could reach 80.1%. Conclusions:PCT can provide additional information about the possible etiology of patients with BSI, especially as high levels often indicate the possibility of GNB bacteremia.
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Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.
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Antioxidants , Biosynthetic Pathways/genetics , Curcumin , Diarylheptanoids , Metabolic Engineering , Plant ExtractsABSTRACT
Objective:To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis.Methods:The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI.Results:A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G +) bacterial infection of patients was significantly higher than that caused by Gram-negative (G -) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G + bacterial infection, the PCT value of patients with G - bacterial infection was higher [μg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHEⅡ score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: ① the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95% CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 μg/L, the sensitivity of diagnosis of G - bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 μg/L, the specificity of diagnosis of G - bacterial infection could reach 81.8%. ② In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHEⅡ score achieved the highest AUC [28 days: 0.791 (95% CI was 0.680-0.902), 60 days: 0.748 (95% CI was 0.645-0.851)]. APACHEⅡ score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95% CI was 0.495-0.725), 60-day AUC: 0.558 (95% CI was 0.450-0.667)]. Conclusion:PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHEⅡ score may perform better in predicting early and late mortality.
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Objective:To investigate the effects of sedatives on the activity of the diaphragm assessed by ultrasound and the timing of extubation in elderly patients after elective surgery.Methods:All 60 eligible elderly patients were randomly divided into three groups: the propofol group, the midazolam group and the control group(n=20, each group). Remifentanil was used in the three groups to keep the Critical Care Pain Observation Tool(CPOT)score less than 3.Patients in the propofol and midazolam groups were given propofol and midazolam sedation respectively, and the Richmond Agitation Sedation Scale(RASS)score was maintained at -2.Diaphragmatic activity was measured, the time from the end of the operation to extubation was recorded, and delirium was evaluated, and the above results were compared with those of the control group, which did not receive sedatives.Results:The activity of the diaphragm was lower in the propofol and midazolam groups than in the control group[(1.10±0.12)cm, (1.17±0.30)cm vs.(1.63±0.25)cm, F=30.170, P=0.000], and there was no significant difference between the propofol group and the midazolam group( t=25.340, P=0.615). There was no significant difference in duration of extubation among the propofol, midazolam and control groups[(1.41±2.08)d, (1.25±1.53)d vs.(1.19±1.40)d, F=0.089, P=0.915]. The incidence of delirium was higher in the midazolam group than in the propofol and control groups[55.0%(11/20), 20.0%(4/20) vs.15.0%(3/20), χ2=5.230, P=0.022, χ2=7.030, P=0.008)], but the difference between the propofol group and control group was not statistically significant( χ2=0.170, P=0.677). Conclusions:The application of sedatives after elective surgery has an effect on the activity of the diaphragm in elderly patients, and the effects of propofol and midazolam are similar.However, propofol and midazolam have no influence on the duration of extubation in elderly patients after elective surgery.Compared with propofol, midazolam increases the incidence of delirium in elderly patients after elective surgery.
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Objective:To compare the early and late predictive value of several critical illness scores (CISs) and biomarkers in patients with bloodstream infection (BSI)-associated pneumonia, and to identify the value of procalcitonin (PCT) in etiological diagnosis.Methods:Patients with at least one positive blood culture within 24 hours admission to department of emergency of China-Japan Friendship Hospital from January 2014 to December 2018 and with final diagnosis of pneumonia were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluationⅡ (APACHEⅡ) scores were calculated based on the first parameters on the day of admission. Differences of various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28-day or 60-day were compared. Receiver operating characteristic (ROC) curve was used to analyze the value of biomarkers in differential diagnosis of pneumonia caused by single bacterial infection, and the predictive value of several CISs and biomarkers on 28-day and 60-day death of patients with pneumonia.Results:Among 540 patients with pneumonia caused by single bacterial infection, 256 (47.4%) patients with Gram-positive bacteria (GPB) infection and 284 (52.6%) with Gram-negative bacteria (GNB) infection. The 28-day mortality was 29.4% (159/540) and the 60-day mortality was 36.3% (196/540). PCT level was significantly higher in patients with GNB infection than that in GPB infected patients [μg/L: 1.99 (0.32, 13.19) vs. 0.45 (0.13, 3.53), P < 0.01]. There were significant differences of CISs and biomarkers between death group and survival group in predicting 28-day and 60-day mortality in BSI-associated pneumonia. ROC curve analysis showed that: ① the optimal cut-off value of PCT in the diagnosis of single bacterial infection was 0.48 μg/L, with the area under ROC curve (AUC) was 0.739 [95% confidence interval (95% CI) was 0.686-0.793]. When PCT value was greater than 4.49 μg/L, the specificity of diagnostic of GNB infection could reach 81.8%, and the positive predictive value (PPV) was 75.0%. When PCT value was greater than 10.16 μg/L, the diagnostic specificity could reach 91.2%. ② In the prediction of 28-day and 60-day mortality, the SOFA score showed highest AUC [28-day: 0.818 (95% CI was 0.768-0.867), 60-day: 0.800 (95% CI was 0.751-0.849)]. SOFA score greater than 8.5 points could help to predict 28-day and 60-day mortality for pneumonia patients with specificity of 90.5% and 91.6%, respectively. AUC of PCT for predicting 28-day and 60-day mortality in patients with BSI associated with pneumonia was 0.637 (95% CI was 0.575-0.700) and 0.628 (95% CI was 0.569-0.688), respectively. When PCT value was greater than 8.15 μg/L, the specificity and negative predictive value (NPV) were 80.2% and 75.1% respectively, and they could reach 80.2% and 68.7% when PCT value was greater than 7.46 μg/L. Conclusion:PCT is more reliable in the identification of pathogen type in BSI-associated pneumonia, while CISs may be more advantageous in the assessment of early and late prognosis.
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Objective@#To investigate the expression of programmed death ligand 1 (PD-L1) in liver cancer tissues and its clinical significance.@*Methods@#The expression levels of PD-L1 in 110 liver cancer tissues, including 95 cases of hepatocellular carcinoma and 15 cases of cholangiocarcinoma were detected by using immunohistochemical staining method, and the relationship between PD-L1 expression and the clinicopathological characteristics of patients with hepatocellular carcinoma was analyzed.@*Results@#Immunohistochemistry results showed that the positive rate of PD-L1 in liver cancer tissues was 69.1% (76/110), and the positive rate of membrane and cytoplasm was 46.4% (51/110) and 22.7% (25/110), respectively. The positive rate of PD-L1 expression in hepatocellular carcinoma was higher than that in cholangiocarcinoma [78.9% (75/95) vs. 6.7% (1/15)], and the difference was statistically significant (χ 2 = 31.693, P < 0.01). The positive expression of PD-L1 was closely associated with the depth of invasion and TNM stage of hepatocellular carcinoma (both χ2 = 4.629, both P = 0.031), but there was no relationship with the patients'age, gender and pathological grade (all P > 0.05). Further analysis showed that protein expression localization of PD-L1 was closely related to the pathological grade in hepatocellular carcinoma (P = 0.013).@*Conclusion@#The positive expression of PD-L1 in hepatocellular carcinoma is closely associated with depth of invasion and TNM stage, which provides a theoretical basis for the immunotherapy of liver cancer targeting PD-L1.
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Objective@#To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance.@*Methods@#A total of 160 patients with chronic heart failure treated at our hospital were recruited, and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity, specificity and accuracy of serum H-FABP, S-100B and NT-proBNP for heart failure detection were compared.@*Results@#Serum levels of H-FABP, S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading(F=9.823, 11.573 and 13.056, P=0.013, 0.000 and 0.000), and serum levels of H-FABP, S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P<0.05). Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels, cardiac function grading and left ventricular end-diastolic diameter(LVEDd)(r=0.527, 0.510 and 0.487, P=0.008, 0.003 and 0.002; r=0.604, 0.496 and 0.533, P=0.006, 0.005 and 0.003), and were negatively correlated with left ventricular ejection fraction(LVEF)(r=-0.536 and-0.528, P=0.005 and 0.008). The sensitivity, specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2%, 91.6% and 95.7%, respectively.@*Conclusions@#Serum levels of H-FABP and S-100B are high in elderly patients with heart failure, and they are correlated with serum NT-proBNP levels, cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.
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Objective To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance.Methods A total of 160 patients with chronic heart failure treated at our hospital were recruited,and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity,specificity and accuracy of serum H-FABP,S-100B and NT-proBNP for heart failure detection were compared.Results Serum levels of H-FABP,S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading (F =9.823,11.573 and 13.056,P =0.013,0.000 and 0.000),and serum levels of H-FABP,S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P＜0.05).Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels,cardiac function grading and left ventricular end-diastolic diameter(LVEDd) (r =0.527,0.510 and 0.487,P =0.008,0.003 and 0.002;r =0.604,0.496 and 0.533,P =0.006,0.005 and 0.003),and were negatively correlated with left ventricular ejection fraction(LVEF) (r =-0.536 and-0.528,P =0.005 and 0.008).The sensitivity,specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2％,91.6％ and 95.7％,respectively.Conclusions Serum levels of H-FABP and S-100B are high in elderly patients with heart failure,and they are correlated with serum NT-proBNP levels,cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.
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Objective To investigate the expression of programmed death ligand 1 (PD-L1) in liver cancer tissues and its clinical significance. Methods The expression levels of PD-L1 in 110 liver cancer tissues, including 95 cases of hepatocellular carcinoma and 15 cases of cholangiocarcinoma were detected by using immunohistochemical staining method, and the relationship between PD-L1 expression and the clinicopathological characteristics of patients with hepatocellular carcinoma was analyzed. Results Immunohistochemistry results showed that the positive rate of PD-L1 in liver cancer tissues was 69.1％(76/110), and the positive rate of membrane and cytoplasm was 46.4％(51/110) and 22.7％(25/110), respectively. The positive rate of PD-L1 expression in hepatocellular carcinoma was higher than that in cholangiocarcinoma [78.9％ (75/95) vs. 6.7％ (1/15)], and the difference was statistically significant (χ2= 31.693, P< 0.01). The positive expression of PD-L1 was closely associated with the depth of invasion and TNM stage of hepatocellular carcinoma (bothχ2= 4.629, both P= 0.031), but there was no relationship with the patients' age, gender and pathological grade (all P> 0.05). Further analysis showed that protein expression localization of PD-L1 was closely related to the pathological grade in hepatocellular carcinoma (P=0.013). Conclusion The positive expression of PD-L1 in hepatocellular carcinoma is closely associated with depth of invasion and TNM stage, which provides a theoretical basis for the immunotherapy of liver cancer targeting PD-L1.
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Objective To explore the clinical value of early fluid resuscitation guided by passive leg-raising test (PLR) combined with transthoracic echocardiography (TTE) in patients with septic shock. Methods A prospective randomized controlled trial (RCT) was conducted. Seventy-four patients with septic shock admitted to China-Japan Friendship Hospital from January 2017 to October 2018 were enrolled. The patients were randomly divided into control group and experimental group with 37 patients in each group. Both groups of patients were treated with broad-spectrum antibiotics empirically, while received fluid resuscitation via the subclavian vein catheter. The patients of control group were given rapid fluid replacement, and those of experimental group received fluid replacement according to result of PLR combined with TTE. The stroke volume (SV) was measured by TTE before and after PLR, volumetric response of patients was judged by stroke volume variation (SVV). If the SVV≥15%, it was considered that there was a volume responsiveness, and fluid loading was given. If SVV﹤15%, it was considered that there was no volume shortage, and the restrictive fluid replacement was given. The goal of fluid resuscitation in both groups were to simultaneously meet the central venous pressure (CVP) of 8-12 mmHg (1 mmHg = 0.133 kPa), mean arterial pressure (MAP) ≥65 mmHg, urine volume ≥ 0.5 mL·kg-1·h-1, and central venous blood oxygen saturation (ScvO2) ≥ 0.70 within 6 hours. Vasoactive drugs were used when the patients could not achieve the treatment goals. The MAP, lactic acid (Lac), oxygenation index (PaO2/FiO2) and ScvO2 of the patients were determined at 6 hours of treatment, and serum C-reactive protein (CRP) and chest CT were reviewed at 48 hours of treatment, and compared with those before treatment. The total hospital stay and the mortality were recorded. Results There was no significant difference in gender, age, body weight and etiological structure between the two groups, which indicated that the baseline data were generally balanced. There was no statistical difference in MAP, Lac, PaO2/FiO2, ScvO2 and CRP before infusion between the two groups. After 6 hours of treatment, the MAP, Lac, PaO2/FiO2 and ScvO2 of the two groups were all better than those before infusion. Except for the difference in MAP between the experimental group and the control group (mmHg: 78.76±5.22 vs. 76.35±6.66, P > 0.05), the other three parameters in the experimental group were significantly better than those in the control group [Lac (mmol/L): 2.52±1.15 vs. 3.89±1.42, PaO2/FiO2 (mmHg):338.14±27.47 vs. 303.35±22.52, ScvO2: 0.70±0.04 vs. 0.63±0.05, all P < 0.01]. After 48 hours of treatment, CRP levels of both groups were lower than those before infusion, and the experimental group was better than the control group (mg/L: 110.12±39.80 vs. 137.98±31.23, P < 0.01). Chest CT showed that the incidence of pulmonary edema in the experimental group was significantly lower than that in the control group [13.5% (5/37) vs. 37.8% (14/37), P < 0.01]. The hospital stay of the experimental group was shorter than that of the control group (days: 21.47±5.58 vs. 28.33±4.93, P < 0.01), but no significant difference in mortality was found between the two groups [18.9% (7/37) vs. 18.9% (7/37), P > 0.05]. Conclusion Compared with the traditional rapid fluid replacement, early fluid resuscitation treatment strategies guided by the PLR combined with TTE, could better improve perfusion and oxygenation level of tissues and organs, avoid pulmonary edema caused by rapid fluid replacement, shorten the hospital stay in patients with septic shock, but had no significant effect on hospital mortality.
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Objective The objectives of this study were to screen and identify monoclonal antibodies against hepatoma stem cells by screening for hepatoma spheroid cells,and to provide candidate therapeutic monoclonal antibodies for targeting cancer stem cells to treat hepatic cancer. Methods Hepatic cancer stem cells were enriched by serum-free suspension culture. Immunofluores-cence,cisplatin resistance assay, Real -time qPCR, subcutaneous tumor formation in nude mice, and other methods were used to screen and identify anti-hepatocarcinoma stem cell monoclonal antibodies. Immunohistochemistry was used to identify the expression of antigen recognized by monoclonal antibody in liver cancer tissues. The antigen was identified by mass spectrometry. Results MH-CC97L cells were able to form cell spheres in serum -free suspension culture and were labeled with PKH26 dye. Flow cytometry showed that the expression of CD90 + in MHCC97L spheroid cells was 3. 4 times higher than that in the parental cells. In the inhibition experiment of serum-free spheroid,6 monoclonal antibodies significantly inhibited MHCC97L cells in serum-free medium,and in-hibitory rates were 54. 67% ,50. 33% ,45. 73% ,42. 26% ,39. 11% ,and 37. 63% ,respectively. The results of immunofluorescence showed that monoclonal antibodies 28C10 and CD90 were colocalized in MHCC97L cells. The results of real-time qPCR showed that the expression of Sox-2 and Oct-4 in MHCC97L 28C10 + cells was significantly higher than those of MHCC97L 28C10 - cells. Flow cytometry showed that the ratio of 28C10 + in MHCC97L cells and its sphere cells were 7. 98% and 10. 7% ,respectively. The ratio of 28C10 + cells was increased by 1. 34 times. The in vitro globing ability and invasive ability of 28C10 + cells obtained by flow cytometry were significantly higher than those of 28C10 - cells. The results of CCK-8 assay showed that 28C10 + cells were resistance to cispla-tin in 28C10 - cells,which are 1. 96 g/ml and 1. 16 g/ml,respectively. Tumorigenic assay showed that 28C10 + cells were inoculated subcutaneously with 2×104 cells into the nude mice,and tumors were formed in 2 months,with 40% of tumor formation rate. Another nude mouse that did not form a tumor had formed a lung metastasis(1/5). Immunohistochemistry showed that the target antigen posi-tive rate of monoclonal antibody 28C10 in hepatic cancer tissues was about 72. 0% (77/107),while it was lowly expressed in adjacent tissues,and the difference was significant. Mass spectrometry showed that the antigen recognized by 28C10 was HSP90α. Conclusion The MHCC97L spheroid cell model is successfully used to identify a monoclonal antibody that specifically recognizes hepatoma stem cells,which provides a foundation for antibody therapy targeting hepatic cancer stem cells.
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Objective To investigate the potential therapeutic effect of luteolin on sepsis-induced ALI and the underlying mechanisms.Methods Total of 50 mice were randomly(random number) divided into five groups:a sham control group,a sepsis-induced ALI group,and three sepsis groups pre-treated with 20,40,and 80 mg/kg body weight luteolin.Mice in the treatment groups were pre-treated with luteolin at the respective oral dose two days before ALI induction.The lungs were isolated for histopathological examinations,and the bronchoalveolar lavage fluid (BALF) was collected for biochemical analyses.Results Luteolin significantly attenuated sepsis-induced ALI.Additionally,luteolin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice.Pulmonary myeloperoxidase (MPO) activity was lower in the luteolin-pre-treated sepsis groups than in the sepsis group.The mechanism underlying the protective effect of luteolin on sepsis is related to the up-regulation of certain antioxidation genes,including inducible nitric oxide synthase (iNOS),cyclooxygenase-2 (COX-2),superoxide dismutases (SODs),and heme oxygenase 1 (HO-1),and the reduction of inflammatory responses through blockage of the activation of the nuclear factor (NF)-κB pathway.Conclusions Luteolin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity,suggesting that luteolin may be a potential therapeutic agent for sepsis-induced ALI.
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As a homeobox transcription factor,MEOX1 can regulate the target genes by binding the specific DNA sequence.MEOX1 not only plays essential roles in cell proliferation,migration and differentiation,but also participates in the formation of skeleton,muscle and blood vessel during embryonic development.Recent studies demonstrate that MEOX1 is over-expressed in breast cancer,lung cancer,ovarian cancer and prostate cancer tissues,which is closely associated with lymph node metastasis and poor prognosis in patients with cancer.Furthermore,MEOX1 can regulate the proliferation and migration of cancer cells,which suggests that it plays an important role in the occurrence and development of tumors.
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Objective To investigate the occurrence of hepatocyte autophagy and the expression of autophagy associated proteins at different time points in sepsis mice model established by cecal ligation and puncture.Methods Fifty male ICR mice aged 6-8 weeks were randomly (random number) divided into 5 groups:CLP 3 h group,CLP 6 h group,CLP 12 h group,CLP 24 h group and control group.The samples were collected at the corresponding time points after operation.Liver function was tested to obtain alanine aminotransferase (ALT) and aspartate aminotransferase (AST).The expression of TNF-α and IL-6 was detected by ELISA,the inflammation of liver tissue by HE staining while the ultrastructure of autophagosome and autolysosome in liver tissue was observed by electron microscopy.Meanwhile,the expression of LC3 and P62 was detected by Western blot.and the location and quantity of autophagosome was observed by Immunofluorescence.SPSS 21.0 was used for statistical analysis.Two independent sample t tests were performed to compare the two groups,and one-way ANOVA was used for comparison between multiple groups.Results ALT and AST increased significantly after CLP,and peaked at 12 h,respectively (137.8 ±11.94) U/L and (475.3 ±57.34) U/L.The expression of IL-6 peaked at 6 h (2589.63 ±27.96) pg/mL,and TNF-α peaked at 3 h (320.21±8.9) pg/mL.HE staining showed activation of Kupffer cells and infiltration of single granulocyte.Electron microscope showed the formation of autophagosome and autolysosome.Compared with the control group,the ratio of LC3 Ⅱ/Ⅰ increased first and then decreased,peaked at 6 h (t=13.35,P＜0.05).The content of P62 protein declined first and then went up,reaching the lowest level at 6 h (t=66.1 l,P＜0.05),contrary to the trend of LC3 Ⅱ/Ⅰ.Immunofluorescence results illustrated that the fluorescence intensity of LC3 reached its high point at 6 h (t=12.52,P＜0.05).Conclusions Autophagy occurred in the liver of sepsis mice model established by cecal ligation and puncture.The formation of autophagosome first increased and then decreased,reaching its peak at 6 h.
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Objective To explore the clinical value of alprostadil in the treatment of hyperlipidemic severe acute pancreatitis (HSAP).Methods A prospective randomized controlled study method was used.56 HSAP cases admitted in emergency intensive care unit (ICU)from May 2015 to November 2016 were enrolled and divided randomly into routine group and alprostadil group using random number method.All the patients in routine group received the routine conservative treatments.Alprostadil group was given both routine treatments and the intravenous injection of 20 μg alprostadil once a day for 7 days.Serum amylase,triglyceride,thromboxane A2 (TXA2) and IL-6 level were detected before,3 d and 8 d after the treatment.MCTSI score and modified Marshall score were calculated.The duration of SIRS,abdominal pain relief time,the start time of enteral nutrition,the average hospitalization days and mortality were recorded.Results There was no significant difference between the two groups on gender,age and body mass.There were no significant statistical differences between the two groups on serum amylase,triglyceride,TXA2,IL-6,MCTSI score and modified Marshall score before treatment,which were all obviously decreased after treatment,and the differences were statistically significant.Serum amylase and triglyceride levels were not statistically different between two groups on 8 days after the treatment,but TXA2 [(85.3 ± 26.8) ng/L vs (138.3 ± 34.3) ng/L],IL-6 [(6.99 ± 1.85)ng/L vs (10.58 ± 2.46) ng/L)],MCTSI score[(2.36 ± 1.10) vs (3.21 ± 1.37)],and modified Marshall score [(1.99 ± 0.57) vs (2.64 ± 0.73)] were all obviously lower than those in routine group,and the differences were statistically significant (P value ＜ 0.05).The duration of SIRS [(5.02 ± 1.81) d vs (6.79 ± 1.17) d],abdominal pain relief time [(4.89 ± 1.47) d vs (6.14 ± 1.58) d],the starting time of enteral nutrition [(4.68 ± 0.86) d vs (6.39 ± 1.11) d],and the average hospitalization ay [(29.30 ±8.61)d vs (34.31 ± 9.33)d] in alprostadil group were obviously shorter than those in routine group,and the differences were statistically significant (P value ＜0.05).But there was no significant difference on hospital mortality.Conclusions Alprostadil can relieve pancreatic injury,reduce organ injury and alleviate abdominal pain early,and promote the recovery of gastrointestinal function by improving pancreatic microcirculation in HSAP.