A Transcriptomic and Metabolomic Study on the Biosynthesis of Iridoids in Phlomoides rotata from the Qinghai-Tibet Plateau.

Phlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1, IDI1, 8-HGO1, and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata. The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata.

Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China.

OBJECTIVES: This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU). DESIGN: Clinical retrospective cross-sectional study. SETTING: A comprehensive teaching tertiary hospital in China. PARTICIPANTS: Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU. MAIN OUTCOME MEASURES: HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded. RESULTS: Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p<0.001). The area under the curve (AUC) value of HBP for diagnosing sepsis was 0.733, which was lower than those corresponding to PCT, CRP and SOFA but higher than those of IL-6, LAC and APACHE II. Multivariate logistic regression analysis identified HBP, PCT, CRP, IL-6 and SOFA as valuable indicators for diagnosing sepsis. A sepsis diagnostic model was constructed based on these indicators, with an AUC of 0.901, a sensitivity of 79.7% and a specificity of 86.9%. CONCLUSIONS: HBP could serve as a biomarker for the diagnosis of sepsis in the ICU. Compared with single indicators, the sepsis diagnostic model constructed using HBP, PCT, CRP, IL-6 and SOFA further enhanced the diagnostic performance of sepsis.

Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation mechanism in Phlomoides rotata from different habitats.

Phlomoides rotata is a traditional medical plant at 3100-5200 m altitude in the Tibet Plateau. In this study, flavonoid metabolites were investigated in P. rotata from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) habitats in Qinghai. The level of kaempferol 3-neohesperidoside, sakuranetin, and biochanin A was high in HN. The content of limocitrin and isoquercetin was high in YS. The levels of ikarisoside A and chrysosplenol D in GL were high. Schaftoside, miquelianin, malvidin chloride, and glabrene in CD exhibited high levels. The results showed a significant correlation between 59 flavonoids and 29 DEGs. Eleven flavonoids increased with altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, and HCT3 genes were crucial in regulating flavonoid biosynthesis. Three enzymes CHS, 4CL, and UFGT, were crucial in regulating flavonoid biosynthesis. This study provided biological and chemical evidence for the different uses of various regional plants of P. rotata.

Flavonoid synthesis in Lamiophlomis rotata from Qinghai-Tibet Plateau is influenced by soil properties, microbial community, and gene expression.

Lamiophlomis rotata is a medicinal plant in Qinghai-Tibet Plateau, in which flavonoid compounds are the major medicinal components. However, it remains unclear how flavonoid metabolism of L. rotata is influenced by soil properties and microbial community. In this study, we collected L. rotata seedlings and rhizosphere soils from five habitats ranging from 3750 to 4270 m of altitude and analyzed the effects of habitat conditions on flavonoid metabolism. The activities of peroxidase, cellulase, and urease were increased with altitude, while those of alkaline phosphatase, alkaline protease, and sucrase were decreased with altitude. Analysis of OTUs showed that the total number of bacterial genera was higher than that of fungal genera. The highest number of fungal genera was 132, and that of bacterial genera was 33 in Batang (BT) town in Yushu County at an altitude of 3880 m, suggesting that the fungal communities may play a critical role in L. rotata rhizosphere soils. Flavonoids in leaves and roots of L. rotata shared a similar pattern, with a trend of increasing levels with altitude. The highest flavonoid content measured, 12.94 mg/g in leaves and 11.43 mg/g in roots, was from Zaduo (ZD) County at an altitude of 4208 m. Soil peroxidases affected quercetin content in leaves of L. rotata, while the fungus Sebacina affected flavonoid content in leaves and roots of L. rotata. The expression of PAL, F3'H, FLS, and FNS genes showed a declining trend in leaves with altitude, while F3H showed an increasing trend in both leaves and roots. Overall, soil physicochemical properties and microbial community affect flavonoid metabolism in L. rotata in Qinghai-Tibet Plateau. The variations in flavonoid content and gene expression as well as their associations with soil factors revealed the complexity of the growth conditions and genetic makeup in L. rotata habitats of Qinghai-Tibet Plateau.

Evaluation of Candidate Reference Genes for Gene Expression Analysis in Wild Lamiophlomis rotata.

Lamiophlomis rotata (Benth.) Kudo is a perennial and unique medicinal plant of the Qinghai-Tibet Plateau. It has the effects of diminishing inflammation, activating blood circulation, removing blood stasis, reducing swelling, and relieving pain. However, thus far, reliable reference gene identifications have not been reported in wild L. rotata. In this study, we identified suitable reference genes for the analysis of gene expression related to the medicinal compound synthesis in wild L. rotata subjected to five different-altitude habitats. Based on the RNA-Seq data of wild L. rotata from five different regions, the stability of 15 candidate internal reference genes was analyzed using geNorm, NormFinder, BestKeeper, and RefFinder. TFIIS, EF-1α, and CYP22 were the most suitable internal reference genes in the leaves of L. rotata from different regions, while OBP, TFIIS, and CYP22 were the optimal reference genes in the roots of L. rotata. The reference genes identified here would be very useful for gene expression studies with different tissues in L. rotata from different habitats.

Aspirin Therapy and 28-Day Mortality in ICU Patients: A Retrospective Observational Study From Two Large Databases.

PURPOSE: Aspirin is widely used in patients in the intensive care unit (ICU); nonetheless, its effects on these patients remain controversial. This retrospective analysis of data from clinical practice investigated the effects of aspirin on 28-day mortality in ICU patients. METHODS: This retrospective study included data from patients in the Medical Information Mart for Intensive Care (MIMIC)-III database and the eICU-Collaborative Research Database (CRD). Patients aged 18 to 90 years and admitted to the ICU were eligible and were assigned to one of two groups according to whether they were given aspirin during their ICU stay. Multiple imputation was used for patients with >10% missing data. Multivariate Cox models and propensity score analysis were used to estimate the association of aspirin treatment with 28-day mortality among patients admitted to the ICU. FINDINGS: In total, 146,191 patients were enrolled in this study, and 27,424 (18.8%) used aspirin. Aspirin treatment in ICU patients, especially in nonseptic patients, was associated with a lower 28-day all-cause mortality on multivariate Cox analysis (eICU-CRD, hazard ratio [HR] = 0.81, [95% CI, 0.75-0.87]; MIMIC-III, HR = 0.72 [95% CI, 0.68-0.76]). Aspirin treatment was associated with lower 28-day all-cause mortality after propensity score matching (eICU-CRD, HR = 0.80 [95% CI, 0.72-0.88]; MIMIC-III, HR = 0.80 [95% CI, 0.76-0.85]). However, on subgroup analysis, aspirin therapy was not associated with a lower 28-day mortality in patients without systemic inflammatory response syndrome (SIRS) symptoms or with sepsis in either database. IMPLICATIONS: Aspirin treatment during the ICU stay was associated with a significantly reduced 28-day all-cause mortality, particularly in patients with SIRS symptoms but without sepsis. In patients with sepsis and with/without SIRS symptoms, beneficial effects were not clear, or more careful patient selection is required.

Dynamic increase in myoglobin level is associated with poor prognosis in critically ill patients: a retrospective cohort study.

Background: Myoglobin is an important biomarker for monitoring critically ill patients. However, the relationship between its dynamic changes and prognosis remains unclear. Methods: We retrospectively enrolled 11,218 critically ill patients from a general and surgical intensive care unit (ICU) of a tertiary hospital between June 2016 and May 2020. Patients with acute cardiovascular events, cardiac and major vascular surgeries, and rhabdomyolysis were excluded. To investigate the early myoglobin distribution, the critically ill patients were stratified according to the highest myoglobin level within 48 h after ICU admission. Based on this, the critically ill patients with more than three measurements within 1 week after ICU admission were included, and latent class trajectory modeling was used to classify the patients. The characteristics and outcomes were compared among groups. Sensitivity analysis was performed to exclude patients who had died within 72 h after ICU admission. Restricted mean survival time regression model based on pseudo values was used to determine the 28-day relative changes in survival time among latent classes. The primary outcome was evaluated with comparison of in-hospital mortality among each Trajectory group, and the secondary outcome was 28-day mortality. Results: Of 6,872 critically ill patients, 3,886 (56.5%) had an elevated myoglobin level (≥150 ng/mL) at admission to ICU, and the in-hospital mortality significantly increased when myoglobin level exceeded 1,000 µg/mL. In LCTM, 2,448 patients were unsupervisedly divided into four groups, including the steady group (n = 1,606, 65.6%), the gradually decreasing group (n = 523, 21.4%), the slowly rising group (n = 272, 11.1%), and the rapidly rising group (n = 47, 1.9%). The rapidly rising group had the largest proportion of sepsis (59.6%), the highest median Sequential Organ Failure Assessment (SOFA) score (10), and the highest in-hospital mortality (74.5%). Sensitivity analysis confirmed that 98.2% of the patients were classified into the same group as in the original model. Compared with the steady group, the rapidly rising group and the slowly rising group were significantly related to the reduction in 28-day survival time (ß = -12.08; 95% CI -15.30 to -8.86; ß = -4.25, 95% CI -5.54 to -2.97, respectively). Conclusion: Elevated myoglobin level is common in critically ill patients admitted to the ICU. Dynamic monitoring of myoglobin levels offers benefit for the prognosis assessment of critically ill patients.

Chinese experts' consensus on the application of intensive care big data.

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts' Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.

Agricultural Application Prospect of Fully Polarimetric and Quantification S-Band SAR Subsystem in Chinese High-Resolution Aerial Remote Sensing System.

The synthetic aperture radar (SAR) is a type of active radar that can obtain polarization scattering information of ground objects, which is an important supplement to optical remote sensing. This paper designs a high-precision quantitative SAR system that combines radiation and polarization calibration processing to achieve a subtle perception of the changes in soil moisture and straw coverage. In Yushu, Jilin, we conducted the first S-band agricultural remote sensing application experiment. The backscattering coefficient was measured under different water content and straw coverage conditions, and the results showed that the backscattering coefficient increased by about 2 dB and 6 dB, respectively. We estimated that the soil water content increased by about 0.01 cm3/cm3, which was consistent with the theoretical analysis. The polarization scattering characteristics also showed significant differences under different straw coverage. The results indicated that S-band quantitative SAR had an excellent response ability to water content and straw coverage, which provided a technical basis for further radar agricultural applications in the future.

Analysis of flavonoid metabolism during fruit development of Lycium chinense.

Lycium chinense is an important medicinal plant in the northwest of China. Flavonoids are the major pharmacological components of L. chinense fruits. However, flavonoid metabolism during fruit development of L. chinense remains to be studied. Here, we analyzed the change of flavonoid contents, enzyme activity, and gene expression during fruit development of L. chinense. We found that flavonoids, anthocyanins, and catechins are the most important components of L. chinense fruits. Flavonoid content was increased with fruit development and was high at the late developmental stage. PAL, CHS, and F3H enzymes played a significant role in flavonoid accumulation in fruits. Transcriptomic analysis showed that anthocyanin pathway, flavonol pathway, flavonoid biosynthesis, and phenylpropanoid synthesis pathway were the major pathways involved in flavonoid metabolism in L. chinense. Gene expression analysis indicated that PAL1 and CHS2 genes were critical for flavonoid metabolism in L. chinense fruits. These discoveries help us understand the dynamic changes in flavonoids during fruit development and enhance the use of L. chinense fruits.

Lymphocyte trajectories are associated with prognosis in critically ill patients: A convenient way to monitor immune status.

Background: Immunosuppression is a risk factor for poor prognosis of critically ill patients, but current monitoring of the immune status in clinical practice is still inadequate. Absolute lymphocyte count (ALC) is not only a convenient biomarker for immune status monitoring but is also suitable for clinical application. In this study, we aimed to explore different trajectories of ALC, and evaluate their relationship with prognosis in critically ill patients. Methods: We retrospectively enrolled 10,619 critically ill patients admitted to a general intensive care unit (ICU) with 56 beds from February 2016 to May 2020. Dynamic ALC was defined as continuous ALC from before ICU admission to 5 days after ICU admission. Initial ALC was defined as the minimum ALC within 48 h after ICU admission. Group-based trajectory modeling (GBTM) was used to group critically ill patients according to dynamic ALC. Multivariate cox regression model was used to determine the independent association of trajectory endotypes with death and persistent inflammation, immunosuppression, catabolism syndrome (PICS). Results: A total of 2022 critically ill patients were unsupervisedly divided into four endotypes based on dynamic ALC, including persistent lymphopenia endotype (n = 1,211; 58.5%), slowly rising endotype (n = 443; 22.6%), rapidly decreasing endotype (n = 281; 14.5%) and normal fluctuation endotype (n = 87; 4.4%). Among the four trajectory endotypes, the persistent lymphopenia endotype had the highest incidence of PICS (24.9%), hospital mortality (14.5%) and 28-day mortality (10.8%). In multivariate cox regression model, persistent lymphopenia was associated with increased risk of 28-day mortality (HR: 1.54; 95% CI: 1.06-2.23), hospital mortality (HR: 1.66; 95% CI: 1.20-2.29) and PICS (HR: 1.79; 95% CI: 1.09-2.94), respectively. Sensitivity analysis further confirmed that the ALC trajectory model of non-infected patients and non-elderly patients can accurately distinguished 91 and 90% of critically ill patients into the same endotypes as the original model, respectively. Conclusion: The ALC trajectory model is helpful for grouping critically ill patients, and early persistent lymphopenia is associated with poor prognosis. Notably, persistent lymphopenia may be a robust signal of immunosuppression in critically ill patients.

Mining of a Clinical Database: The Interpretation of Intense Serial Procalcitonin in the Prediction for Bloodstream Infection.

Background: Procalcitonin (PCT) is a promising biomarker for predicting infection. Bloodstream infection (BSI) is usually a deteriorating stage of sepsis. The purpose of this study was to explore the predictive value of intense serial PCT assays for BSI in the intensive care unit (ICU). Methods: This study was a retrospective study based on a clinical database. We analyzed the data of critically ill patients from February 2016 to May 2020. The patients who received PCT assays and blood cultures (BCs) were classified into four groups according to the BCs: (i) BC negative, (ii) bacteria positive, (iii) fungi-positive, and (iv) combined-positive, and the patients with bacteremia were further subdivided into Gram+ and Gram- bacteremia. Results: The database included 11,219 patients. There were 3,593 patients who met the criteria for the analysis. The PCT concentration differed significantly across BC groups (p < 0.0001). The fluctuation of PCT significantly increased in the BC positive groups (p < 0.0001). According to the receiver operating characteristic (ROC), the optimum cutoff of the fluctuation of PCT was around 8 ng/ml for predicting BSI. Conclusion: Our study indicated that the fluctuation of PCT could be an indicator for screening BSI, but less accurate for Gram-positive infections. With a fluctuation of PCT less than 8 ng/ml, BSI should not be a rational cause for sepsis exacerbating.

Kidney Injury in a Hemodilution Model of Hemorrhagic Shock and Fluid Resuscitation.

BACKGROUND: Fluid therapy is indispensable in treating patients with hemorrhagic shock. However, fluid overload correlates with kidney injury in patients with hemorrhagic shock. We hypothesized that hemodilution after fluid treatment contributes to the kidney injury. METHODS: An animal model was established to mimic different severity of hemodilution, through resuscitating hemorrhagic shock with mixture of blood and lactated Ringer's solution (LR) in different ratios. A total of 20 rats were divided into the following four groups, the Sham group, Mild group, Moderate group, and Severe group. In the Sham group, rats were anesthetized and catheterized only. In the other three groups, shock was induced by extracting 40% of the estimated circulating blood. One hour later, rats were resuscitated with a mixture of blood and LR with ratio 1:0 in the Mild group, 0.5:0.5 in the Moderate group, and 0:1 in the Severe group. The histology of the kidneys was observed with hematoxylin and eosin (HE) staining. The mitochondria membrane potential ψ and adenosine triphosphate (ATP) production of the kidneys were measured. The serum creatinine (SCr) and blood urine nitrogen (BUN) were measured. RESULTS: Renal tubular lumina dilation and mild interstitial edema occurred in the Mild group with HE staining. Proximal convoluted tubule damage, including tubular casts, narrow renal tubular lumina, and interstitial edema occurred in the Moderate group and Severe group. Mitochondrial JC-1 and ATP production decreased as hemodilution progressed. SCr and BUN increased in the Moderate group and Severe group. CONCLUSIONS: The hemodilution post hemorrhagic shock and fluid resuscitation led to kidney injury.

[Clinical study of D-lactate and intestinal fatty acid binding protein in evaluating disease severity and prognosis of ICU patients: secondary analysis of a prospective, multicenter clinical study].

OBJECTIVE: To analyze the relationship between D-lactate, intestinal fatty acid binding protein (I-FABP) and the severity as well as the prognosis of patients in intensive care unit (ICU). METHODS: Using a retrospective approach, the data derived from a prospective, randomized, single-blind, multicenter clinical study published earlier by our group were further analyzed to evaluate the effect of fat-modified enteral nutrition (EN) suspension on the intestinal barrier in ICU patients. In this study, a total of 141 patients were recruited from 7 ICUs in South China, and 15 healthy volunteers were included as healthy control group. Clinical data of patients were collected, including gender, age, disease severity related indicators such as acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), C-reactive protein (CRP) and initial ICU diagnosis, as well as prognostic indicators such as length of stay in ICU, length of stay in hospital and prognosis of patients at 28 days. To compare the difference of serum D-lactate and I-FABP between ICU patients and healthy control group on day 0 (the day before EN reached 500 mL) and day 5 (EN ≥ 2 092 kJ/d for 5 days). According to the hemodynamic and/or mechanical ventilation status on day 5 (compared with day 0), 141 patients were divided into the improvement group (101 cases) and the non-improvement group (40 cases), and the changes of D-lactate and I-FABP in the two groups were observed. Spearman correlation analysis was used to analyze the correlation between serum D-lactate, I-FABP and the severity of the disease, as well as the predictive value of dynamic changes of D-lactate and I-FABP on the prognosis of 28 days. RESULTS: Compared with the healthy volunteers, the serum D-lactate and I-FABP levels of ICU patients on day 0 were significantly increased [D-lactate (mg/L): 10.82 (3.31, 25.48) vs. 6.63 (1.54, 17.70), I-FABP (ng/L): 519.60 (159.06, 1 362.14) vs. 84.40 (30.78, 108.57), both P < 0.01], and D-lactate and I-FABP on day 5 were both decreased compared with the levels on day 0, but still higher than the healthy volunteers. I-FABP in the improvement group was significantly lower than that in the non-improvement group on day 0, and there was no significant difference in D-lactate levels between the two groups, D-lactate and I-FABP in both groups were significantly lower on day 5 than those on day 0, and D-lactate and I-FABP in the improvement group on day 5 were significantly lower than those in the non-improvement group [D-lactate (mg/L): 7.61 (1.71, 27.22) vs. 9.38 (2.09, 20.56), I-FABP (ng/L): 378.65 (152.56, 864.62) vs. 521.21 (205.93, 1 413.11), all P < 0.05]. Correlation analysis showed that D-lactate was significantly positively correlated with APACHE II score and SOFA score on day 0 and day 5 (R12 = 0.367, P < 0.001; R22 = 0.240, P = 0.012); I-FABP was significantly positively correlated with APACHE II score on day 0 (R2 = 0.264, P = 0.004); D-lactate on day 5 and I-FABP on day 0 and day 5 were significantly negatively correlated with prognosis on day 28 (R12 = -0.203, P = 0.022; R22 = -0.208, P = 0.023; R32 = -0.211, P = 0.021). The area under curve (AUC) analysis showed that D-lactate on day 5 and I-FABP on day 0 and day 5 had independent predictive value for 28-day prognosis, with AUC of 0.634, 0.638 and 0.652, P values of 0.023, 0.024 and 0.017, 95% confidence intervals (95%CI) of 0.533-0.734, 0.523-0.754 and 0.525-0.778, respectively. When the cut-off values were 7.71 mg/L, 593.55 ng/L and 468.10 ng/L, the sensitivity were 51.5%, 68.5% and 75.3%, and the specificity were 91.0%, 60.0% and 60.0%, respectively. CONCLUSIONS: Serum D-lactate and I-FABP were increased significantly and decreased with the improvement of the condition, and these two molecular biomarkers have certain value in predicting the prognosis of ICU patients.

Fabrication and Characterization of Thermal-responsive Biomimetic Small-scale Shape Memory Wood Composites with High Tensile Strength, High Anisotropy.

Intelligent responsive materials have become one of the most exciting fields in the research of new materials in the past few decades due to their practical and potential applications in aerospace, biomedicine, textile, electronics, and other relative fields. Here, a novel thermal-responsive biomimetic shape memory wood composite is fabricated utilizing polycaprolactone-based (PCL) shape-memory polymer to modify treated-wood. The shape memory wood inherits visual characteristics and the unique three-dimension structure of natural wood that endows the shape memory wood (SMW) with outstanding tensile strength (10.68 MPa) at room temperature. In terms of shape memory performance, the shape recovery ratio is affected by multiple factors including environment temperature, first figuration angle, cycle times, and shows different variation tendency, respectively. Compared with shape recovery ratio, the shape fixity ratio (96%) is relatively high and stable. This study supplies more possibilities for the functional applications of wood, such as biomimetic architecture, self-healing wood veneering, and intelligent furniture.

[Correlation between oxidative stress factors and prognosis of patients with sepsis].

OBJECTIVE: To investigate the relationship between plasma oxidative stress factors levels and organ damage parameters as well as prognosis in patients with sepsis. METHODS: A case-control study was conducted. Twenty-five patients admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from March to December in 2016 and diagnosed as sepsis were enrolled as study subjects. Another 15 patients without sepsis admitted to surgical ICU in the same period were enrolled as controls. General demographic data, main diagnoses, acute physiology and chronic health evaluation II (APACHE II) score within 24 hours, clinical laboratory indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT), white blood count (WBC)] and oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO)] as well as length of ICU stay, total hospital stay and 28-day mortality were recorded. Spearman or Pearson correlation method was used to analyze the correlation between oxidative stress indicators and organ damage indicators as well as prognosis in patients with sepsis. Receiver operator characteristic (ROC) curve was plotted to evaluate the predictive value of oxidative stress indicators for 28-day mortality in patients with sepsis. RESULTS: The length of ICU stay in sepsis group was significantly longer than that in non-sepsis group [days: 7.0 (5.5, 11.0) vs. 4.0 (1.0, 11.0), P < 0.05], and AST, BUN, CRP, PCT, plasma MDA and NO levels were significantly higher than those in non-sepsis group [AST (U/L): 50.76±19.53 vs. 28.53±14.02, BUN (mmol/L): 9.99±5.26 vs. 6.97±4.32, CRP (mg/L): 109.28±42.79 vs. 60.33±46.68, PCT (µg/L): 5.4 (0.3, 24.0) vs. 0.6 (0.1, 1.5), MDA (ng/L): 488.31±76.68 vs. 399.30±50.23, NO (ng/L): 5.08±0.89 vs. 4.42±0.88, all P < 0.05]. There was no significant difference in gender, age, APACHE II score, total hospital stay, 28-day mortality, ALT, SCr, WBC or plasma SOD activity between the two groups. The correlation analysis between oxidative stress parameters and organ damage parameters as well as prognosis in patients with sepsis showed that MDA and NO were positively correlated with SCr (r value was 0.426 and 0.431, respectively, both P < 0.05), and there was a positive correlation between MDA and NO (r = 0.990, P < 0.01); plasma SOD activity was negatively correlated with 28-day mortality (r = -0.468, P < 0.05), while MDA and NO levels were positively correlated with 28-day mortality (r value was 0.598 and 0.611, respectively, both P < 0.01). ROC curve analysis showed that plasma SOD, MDA and NO levels had a good independent predictive effect on 28-day mortality, the area under ROC curve (AUC) was 0.816±0.087, 0.904±0.078 and 0.912±0.071, and the best cut-off value was 40.76% (sensitivity 68.4%, specificity 100%), 487.93 ng/L (sensitivity 83.3%, specificity 89.5%) and 5.31 ng/L (sensitivity 83.3%, specificity 89.5%), respectively. CONCLUSIONS: The plasma levels of oxidative stress factors in patients with sepsis are significantly increased, which is closely related to organ damage and poor prognosis. The plasma SOD, MDA and NO levels can be used as independent bio-marker to predict the 28-day mortality of patients with sepsis.

Fluid Removal With Ultrasound Guided Protocol Improves the Efficacy and Safety of Dehydration in Post-Resuscitated Critically Ill Patients: A Quasi-Experimental, Before and After Study.

Fluid overload is associated with increased morbidity and mortality in critically ill patients. However, researches rarely study the precise start or end point of fluid removal and no protocol was developed to control the fluid removal process. We hypothesized that individualized fluid removal with ultrasound-guided protocol could improve the efficacy and safety of fluid removal in post-resuscitated critically ill patients. A quasi-experimental, before and after trial was conducted to identify the benefits of ultrasound-guided fluid removal. Fluid removal was performed either following the doctor's experience in Control group, or abiding the ultrasound guided protocol in Ultrasound group. The study end points were the start time, end time, length of fluid removal, and the complications related to fluid removal. A total of 85 subjects were finally analyzed in this study. The fluid removal was started earlier, completed quicker and ended earlier (21.0 ±â€Š14.6 h vs. 35.1 ±â€Š26.5 h, 49.8 ±â€Š32.6 vs. 93.0 ±â€Š42.8 h, 69.0 ±â€Š32.2 h vs. 126.4 ±â€Š52.5 h, P < 0.05) in Ultrasound group than in Control. The subjects had more daily negative fluid balance and urine output (-990.4 ±â€Š636.1 mL vs. -723.6 ±â€Š549.5 mL, 2425.8 ±â€Š886.7 mL vs. 1560.7 ±â€Š1125.3 mL, P < 0.05) in Ultrasound group. The time of lung B-lines to reduce to zero was shorter and B-line at the end point was less (49.5 ±â€Š36.6 h vs. 75.6 ±â€Š58.8 h, 0[1] vs. 0[0], P < 0.05) in Ultrasound group. The length of intensive care unit stay in shock subgroup had a tendency to shorten (96.1 ±â€Š61.5 h vs. 174.6 ±â€Š132.0 h, P > 0.05) in Ultrasound group. We concluded that fluid removal with individualized ultrasound-guided protocol improves the efficacy and safety of dehydration in critically ill patients.

Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.

MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death. Interestingly, following the identification of CEBPD-induced miRNAs, we found that miR-744, miR-3154 and miR-3162 could target CpG islands in the 5'-flanking region of the CEBPD gene. We previously demonstrated that the Yin Yang 1 (YY1)/polycomb group (PcG) protein/DNA methyltransferase (DNMT) complex is important for CCAAT/enhancer binding protein delta (CEBPD) gene inactivation; we further found that Argonaute 2 (Ago2) interacts with YY1 and binds to the CEBPD promoter. The miRNA/Ago2/YY1/PcG group protein/DNMT complex linked the inactivation of CEBPD and genes adjacent to its 5'-flanking region, including protein kinase DNA-activated catalytic polypeptide (PRKDC), minichromosome maintenance-deficient 4 (MCM4) and ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2), upon bortezomib treatment. Moreover, we revealed that miRNA binding is necessary for YY1/PcG group protein/DNMT complex-mediated epigenetic gene silencing and is associated with bortezomib-induced methylation on genomic DNA. The present study successfully characterized the interactions of the miRNA/Ago2/YY1/PcG group protein/DNMT complex and provided new insights for miRNA-mediated epigenetic regulation in bortezomib-induced leukemic cell arrest and cell death.

[Evaluation of volume overload in critical patients by monitoring change of cardiac output under bed head raising combined with passive leg raising].

OBJECTIVE: To investigate whether the change of cardiac output (CO) with bed head raising (BHR) combined with passive leg raising (PLR) can be used to assess volume overload in critical patients. METHODS: A prospective observational diagnostic trial was designed. The patients who underwent fluid resuscitation 6 hours or more, and admitted to intensive care unit (ICU) of Meizhou People's Hospital in Guangdong Province from January to December in 2016 were enrolled. Volume overload were identified with the criteria including the increasing of pulmonary rales, the higher levels of N-terminal brain natriuretic peptide (NT-proBNP) and new pulmonary exudates in chest radiograph. CO and heart rate (HR) were monitored with impedance cardiography at supine position and BHR by 30degree angle (BHR30), 60degree angle (BHR60), and PLR in all patients. The changes of CO (ΔCO30, ΔCO60, ΔCOPLR) and HR (ΔHR30, ΔHR60, ΔHRPLR) were calculated at different positions. The receiver operating characteristic curve (ROC) was used to evaluate the predictive values of ΔCO30, ΔCO60 and combination of ΔCO60 and ΔCOPLR on volume overload. RESULTS: A total of 62 patients were enrolled in this study, with 44 males and 18 females, age of (58.9±15.9) years, a body mass index of (22.7±2.4) kg/m2, and an acute physiology and chronic health evaluation II (APACHE II) score of 18.7±4.4. The CO of 32 patients with volume overload was significantly increased at BHR30 or BHR60 compared with supine position [ΔCO30 was (14.5±11.5)%, ΔCO60 was (26.9±17.5)%, both P < 0.01], and the ΔCO60 was increased more than the ΔCO30 (P < 0.01); while CO was slightly decreased after PLR, ΔCOPLR was (-8.4±11.3)% (P > 0.05). There was no consistent change of CO at BHR30 or BHR60 compared with supine position in 30 patients without volume overload, ΔCO30 was (-3.4±9.1)% (P < 0.05), ΔCO60 was (-2.4±14.0)% (P > 0.05), while CO was significantly increased after PLR, ΔCOPLR was (12.4±11.3)% (P < 0.01). There was no significant change of HR after BHR and PLR in patients with volume overload and non volume overload. ROC curve showed that when the cut-off value of ΔCO30≥3.3%, the area under ROC curve (AUC) was 0.903±0.039, the sensitivity was 90.6%, the specificity was 80.0%, and the accuracy was 85.5% for predicting volume overload; when the cut-off value of ΔCO60≥5.6%, the AUC was 0.911±0.036, the sensitivity was 96.9%, the specificity was 73.3%, and the accuracy was 85.5% for predicting volume overload. If volume overload was assessed by the increase of ΔCO60 combining with the decrease of ΔCOPLR, the AUC was 0.928±0.034, the optimal cut-off value for the new combined predictive indicator in predicting volume overload was -0.008, and the sensitivity, specificity, accuracy was 96.9%, 83.3%, 90.3%, respectively, and its evaluation effect is better than the use of ΔCO30 or ΔCO60 alone. CONCLUSIONS: The change of CO with BHR combined with PLR can be used to accurately evaluate volume overload in patient with critically illness.

[Clinical value of lung ultrasound in the late goal-directed fluid removal in critically ill patients underwent fluid resuscitation].

OBJECTIVE: To investigate the clinical value of lung ultrasound in the late goal -directed fluid removal in critically ill patients underwent fluid resuscitation. METHODS: A prospective study was conducted. Forty patients underwent fluid resuscitation were enrolled in the Department of Surgical Intensive Care Unit of The First Affiliated Hospital of Sun Yat-sen University from Jan 2015 to June 2015. Lung and heart ultrasound were conducted for lung B-lines and left ventricular ejection fraction (EF). Serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), central venous pressure (CVP) and serum creatinine were also measured and fluid balance was recorded in all patients enrolled. RESULTS: Among the 40 patients enrolled, 35 patients survived and 5 died. In patients survived, B-lines reached its peak at 12(30)h after admitted to ICU. It started to decrease instantly after the peak and reached zero at (39±34) h. A higher peak was followed with more fluids to be removed later and longer ICU stay (P<0.01). Moreover, when compared with the survivors, B-lines in death reached a higher peak[7(8) vs 3(4), P<0.01]and without the tendency to drop down. EF was lower in death than in survivor (44.5%±3.5% vs 69.2%±11.0%, P<0.05). A lower EF was found to be followed with a higher peak of B-lines. The peak time of NT-proBNP and clinical dehydration treatment were later than the peak time of B-lines in survivors. CONCLUSIONS: Fluid overloading occurs in late stage after resuscitation in critically ill patients. Lung ultrasound B-lines, which is more sensitive than the NT-proBNP and CVP, could help to monitor the patient's fluid status and guide the late goal-directed fluid removal.