TSPO exacerbates acute cerebral ischemia/reperfusion injury by inducing autophagy dysfunction.

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.

Performance Optimization of FA-GGBS Geopolymer Based on Response Surface Methodology.

Many scholars have focused on the workability and mechanical properties of fly ash (FA)- ground granulated blast furnace slag (GGBS) geopolymer. To enhance the compressive strength of geopolymer, zeolite powder was added in the present study. A series of experiments were carried out to investigate the effect of using zeolite powder as an external admixture on the per-formance of FA-GGBS geopolymer, 17 sets of experiments were designed and tested to deter-mine the unconfined compressive strength based on the response surface methodology, and then, the optimal parameters were obtained via modeling of 3 factors (zeolite powder dosage, alkali exciter dosage, and alkali exciter modulus) and 2 levels of compressive strength (3 d and 28 d). The experimental results showed that the strength of the geopolymer was the highest when the three factors were 13.3%, 40.3%, and 1.2. Finally, a combination of scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and 29Si nuclear magnetic resonance (NMR) analysis was used to conduct micromechanical analysis and explain the reaction mechanism from a microscopic perspective. The SEM and XRD analysis revealed that the microstructure of the geopolymer was the densest when the zeolite powder was doped at 13.3%, and the strength increased accordingly. The NMR and Fourier transform infrared spectroscopy analyses revealed that the absorption peak wave number band shifted toward the lower wave number band under the optimal ratio, and the silica-oxygen bond was replaced by an aluminum-oxygen bond, which generated more aluminosilicate structures.

Chlorogenic acid ameliorates obesity by preventing energy balance shift in high-fat diet induced obese mice.

BACKGROUND: Chlorogenic acid is a type of phenolic acid found in many plants. Chlorogenic acid has an anti-obesity effect with an unclear mechanism. The present study aimed to investigate the regulatory effect of chlorogenic acid on energy balance in high-fat diet (HFD) induced obese C57BL/6J mice administrated 100 mg kg-1 chlorogenic acid for 13 weeks. RESULTS: The consumption of chlorogenic acid ameliorated HFD induced obesity. Chlorogenic acid did not change the physical activity but significantly decreased food intake and increased body temperature, thermal dissipation and brown adipose tissue activity. Moreover, chlorogenic acid improved glucose tolerance but had a moderate impact on other blood indices. Additionally, chlorogenic acid failed to restore the microbiota change associated with HFD induced obesity, but modified the gut bacterial composition in a unique way. CONCLUSION: Supplementation with chlorogenic acid can improve HFD induced obesity and associated glucose intolerance mainly via regulating food intake and energy expenditure. © 2020 Society of Chemical Industry.

Metabolic acidosis in critically ill patients with cirrhosis: Epidemiology and short-term mortality risk factors.

BACKGROUND/AIMS: Metabolic acidosis is a common complication in patients with cirrhosis at the intensive care units (ICUs) and associated with increased mortality. The aim of our research was to explore the epidemiology and risk factors of metabolic acidosis in critically ill patients with cirrhosis. MATERIALS AND METHODS: A total of 975 patients with cirrhosis were selected into our study, and all participants were followed up for at least 28 days. Cox regression model and machine-learning algorithm were used to identify the importance of different risk factors, respectively. Finally, an improved prognostic model as Model for End-stage Liver Disease and metabolic acidosis (MELD-MA) was developed. RESULTS: Among the 975 patients with liver cirrhosis, 506 had metabolic acidosis, including 257 patients who had decompensated metabolic acidosis at ICU admission. The 28-day mortality was 41% (206/506) in patients with metabolic acidosis. Bilirubin (hazard ratio (HR): 1.023, 95% confidence interval (CI): 1.011-1.036), international normalized ratio (HR: 1.527, 95% CI: 1.332-1.750), pH (HR: 0.173, 95% CI: 0.047-0.640), BE-Lac (HR: 0.907, 95% CI: 0.868-0.948), and BE-Na (HR: 0.923, 95% CI: 0.859-0.991) were considered as independent prognostic parameters for 28-day mortality. MELD-NA had significantly higher discrimination (area under the receiver operating characteristic curve 0.79) than MELD and Child-Pugh score. CONCLUSION: Critically ill patients with cirrhosis have a high mortality rate and poor prognosis because of the high prevalence of metabolic acidosis. Lactic acidosis is the worst prognosis of all types of metabolic acidosis. MELD-MA performs well on the short-term mortality assessment in critically ill patients with cirrhosis and metabolic acidosis.

Prognostic value of serum lactate kinetics in critically ill patients with cirrhosis and acute-on-chronic liver failure: a multicenter study.

Lactate clearance (Δ24Lac) was reported to be inversely associated with mortality in critically ill patients. The aim of our study was to assess the value of Δ24Lac for the prognosis of critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF). We analysed 954 cirrhotic patients with hyperlactatemia admitted to intensive care units (ICUs) in the United States and eastern China. The patients were followed up for at least 1 year. In the unadjusted model, we observed a 15% decrease in hospital mortality with each 10% increase in Δ24Lac. In the fully adjusted model, the relationship between the risk of death and Δ24Lac remained statistically significant (hospital mortality: odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.78- 0.90, p < 0.001; 90-day mortality: hazard ratio [HR] 0.94, 95%CI 0.92- 0.97, p < 0.001; for Δ24Lac per 10% increase). Similar results were found in patients with ACLF. We developed a Δ24Lac-adjusted score (LiFe-Δ24Lac), which performed significantly better in the area under the receiver operating characteristic curves (AUROCs) than the original LiFe score for predicting mortality. Lactate clearance is an independent predictor of death, and the LiFe-Δ24Lac score is a practical tool for stratifying the risk of death.

Model for end-stage liver disease and pneumonia: An improved scoring model for critically ill cirrhotic patients with pneumonia.

BACKGROUND/AIMS: Critically ill patients with cirrhosis with pneumonia are at an increased risk for mortality. Only a few accurate predictive models are existing specific to these patients. The aim of the present study was to compare the existing prognostic models and to develop an improved mortality risk model for patients with cirrhosis and pneumonia. MATERIALS AND METHODS: A total of 231 patients were enrolled in our study (70% training and 30% validation cohorts). All participants were followed up for at least 21 days. Model for End-stage Liver Disease and Pneumonia (MELD-P) was derived by the Cox proportional hazards model. The performances of prognostic scoring systems were compared by calculation of the area under the receiver operating characteristic (AUROC) curve. RESULTS: MELD-P showed better discriminative capabilities than existing scoring systems. Four clinical variables, including loge bilirubin (hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.01-1.73), loge international normalized ratio (HR 3.57, 95% CI 1.30-9.78), loge pulse oxygen saturation/fraction of inspired oxygen (HR 0.38, 95% CI 0.14-0.99), and vasopressors used (HR 3.72, 95% CI 1.85-7.49), were considered as independent prognostic values associated with 21-day mortality. MELD-P had AUROC curve values of 0.78 (95% CI 0.71-0.84) in predicting in-hospital mortality, 0.78 (95% CI 0.70-0.84) at 21-day, 0.88 (95% CI 0.82-0.93) at 14-day, and 0.87 (95% CI 0.81-0.92) at 7-day. A similar result was obtained in validation cohort. CONCLUSION: MELD-P, as the first model specifically designed to evaluate the risk of mortality in critically ill patients with cirrhosis and pneumonia, performs well on the mortality assessment of short-term mortality.

Prognostic value of international normalized ratio to albumin ratio among critically ill patients with cirrhosis.

BACKGROUND AND AIM: Critically ill patients with cirrhosis are at an increased risk of mortality. Our study aimed to externally validate the ability of the prothrombin time-international normalized ratio to albumin ratio (PTAR), an objective and simple scoring system, to predict 90-day mortality in critically ill patients with cirrhosis. PATIENTS AND METHODS: A total of 865 patients were entered into the study, and all the participants were followed up for at least 90 days. Clinical parameters on the first day of intensive care unit admission were included to compare survivors with nonsurvivors. RESULTS: After multivariable adjustment, the association between the risk of 90-day mortality and PTAR remained statistically significant with a hazard ratio of 2.71 (95% confidence interval: 1.99-3.68). The PTAR score showed good discrimination ability for predicting 90-day mortality with an area under receiver operating characteristic curve of 0.72 (95% confidence interval: 0.68-0.75). To improve its feasibility, we regrouped the PTAR scores into three levels of risk (low risk: <0.55, intermediate risk: 0.55-1.00, and high risk: ≥1.00); the 90-day mortality rates were 20.1% (74/368), 41.7% (168/403), and 73.4% (69/94), respectively. CONCLUSION: The PTAR score system is a convenient and practical tool for predicting the prognosis of critically ill patients with cirrhosis.

Determination of taxifolin in Polygonum orientale of different storage period / 中国中药杂志

<p><b>OBJECTIVE</b>To find out the correlation between the content of taxifolin in Polygonum orientale and the storage time.</p><p><b>METHOD</b>HPLC was used to determine taxifolin. The chromatographic condition was as following: Diamonsil C18 column (4.6 mm x 200 mm, 5 microm), mobile phase acetonitrile -0.1% phosphoric acid (gradient elution), the detection wavelength 290 nm and flow rate 1.0 mL x min(-1), the column temperature 30 degrees C.</p><p><b>RESULT</b>The injection volume of taxifolin was in good linearity within 0.07 and 0.35 microg, the average recovery was 99.7% with RSD 0.2%. Taxifolin content was 0.84, 1.36, 1.75, 1.99 mg x g(-1) corresponding to storage time of 10, 7, 6, 5 years, respectively.</p><p><b>CONCLUSION</b>The content of taxifolin decreased with the storage time. When the storage period is more than six years, the content is lower than that required by Chinese Pharmacopoeia (2010 version). This method has a good repeatability and accuracy, it provides a scientific reference for clinical use and quality evaluation of P. orientale.</p>

Simultaneous determination of four flavones in root and stem of Cudrania tricuspidata and C. cochinchinensis by HPLC-DAD / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a HPLC-DAD method for the determination of axifolin, naringenin, quercetin and kaempferol in Cudrania tricuspidata and C. cochinchinensis in order to provide a scientific reference for species identification and quality evaluation, by establishing.</p><p><b>METHOD</b>The determination was performed by HPLC-DAD on an Agilent C18 column (4.6 mm x 150 mm, 5 microm) by gradient elution (0-15 min, 35%-50% A; 15-30 min, 50% - 65% A) using methanol (A) and 0.1% phosphoric acid (B) as the mobile phase. The flow rate was 1 mL x min(-1). The detection wavelength was 290 nm for taxifolin and naringenin, 365 nm for quercetin and kaempferol with column temperature at 30 degrees C.</p><p><b>RESULT</b>The content of axifolin and quercetin in the root of C. tricuspidata were remarkably higher than that in the root of C. cochinchinensis, and the content in stem of C. tricuspidata was also higher than that in the stem of C. cochinchinensis, the content of axifolin and quercetin was variable in different species. The content of naringenin and kaempferol in the root of C. cochinchinensis was visibly higher than that in the root of C. tricuspidata, and the content in the stems of the two herbs was similar, the content of naringenin and kaempferol was visibly variable in different medicinal parts of the herb, but similar between the two herbs.</p><p><b>CONCLUSION</b>There's some difference of the content of the four ingredients in different medicinal parts and different herbs, so clinical use should not be confused.</p>

Effect comparison of two kinds of therapeutic methods of olecranon fracture / 中国骨伤

<p><b>OBJECTIVE</b>To compare the effects of olecranon plate and tension band in the treatment of olecranon fracture.</p><p><b>METHODS</b>Sixty-three patients with olecranon fracture were treated with olecranon plate and tension band. Thirty-five patients (21 male and 14 female, aged from 15 to 62 years, with an average of 48.9 years) were involved in tension band group and 28 patients (20 male and 8 female, aged from 25 to 67 years, with an average of 50.6 years)were involved in plate group. According to the Delee, JC classification in 1984, there were type 1A in 5 cases, type 1B in 8 cases, type 2 in 17 cases, type 3 in 7 cases and type 4 in 1 case in tension band group; there were type 1A in 3 cases, type 1B in 5 cases, type 2 in 6 cases, type 3 in 11 cases and type 4 in 3 cases in plate group.</p><p><b>RESULTS</b>Sixty-three cases were all followed up from 6 to 15 months. According to the criterion of PANG Gui-gen, the results were excellent in 20 cases, good in 7 cases, fair in 1 case and no bad in plate group; the results were excellent in 23 cases, good in 10 cases, fair in 21 case and no bad in tension band group. The therapeutic effect of two groups has no significantly statistic difference.</p><p><b>CONCLUSION</b>Both olecranon plate and tension band are the effective treatments for olecranon fracture. The selection of two methods should depend on to the state of fracture.</p>