Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Characteristic Analysis of a Chipless RFID Sensor Based on Multi-Parameter Sensing and an Intelligent Detection Method.

Chipless radio frequency identification (RFID) technology has been widely used in the field of structural health monitoring (SHM), but most of the current research mainly focuses on the detection of mechanical properties and there are few studies on the multi-physical parameters (for example, temperature and humidity) in the climatic environment around the structure. Thus, it is necessary to design a small and compact sensor for multi-parameter detection. This paper proposes a multi-parameter chipless RFID sensor based on microstrip coupling, which supports 4-bit ID code and integrates two detection functions of temperature and humidity. Through linear normalization fitting, the sensitivity of the sensor is about 2.18 MHz/RH in the ambient relative humidity test and the sensitivity of the sensor is about 898.63 KHz/°C in the experimental test of water bath heating from 24.6 °C to 75 °C. In addition, this paper proposes an engineering application detection method, designs a lightweight dynamic spectrum detection and wireless transmission platform based on a lightweight vector network analyzer (VNA) and realizes the real-time extraction and transmission of RFID spectrum sensing data. The means are more flexible and economical than traditional experimental scenarios.

Total Synthesis of Sarpagine Alkaloid (-)-Normacusine B.

An asymmetric total synthesis of the sarpagine alkaloid (-)-normacusine B is presented. Salient features of this synthesis include a photocatalytic nitrogen-centered radical cascade reaction to assemble the tetrahydrocarbolinone skeleton, a titanium-mediated intramolecular amide-alkene coupling to construct the bridged azabicyclo[3.3.1]nonane moiety, and a nickel-catalyzed reductive Heck coupling to assemble the azabicyclo[2.2.2]octane ring system.

Characterization of the binding motif for the T3SS master regulator LcrF in Yersinia pseudotuberculosis.

LcrF is the master regulator that positively regulates the Ysc type III secretion system (T3SS) in Yersinia and shares a high similarity with the DNA-binding domain of the T3SS master regulator ExsA in Pseudomonas aeruginosa. Based on these features, bioinformatics analysis has predicted a putative LcrF-binding site in its target promoters. Here, we experimentally characterized its binding motif. An adenine-rich LcrF-binding region in the lcrG promoter sequence, a typical regulatory target of LcrF, was first confirmed. To obtain detailed information, this binding region was cloned into a synthetized promoter and mutations in this region were further constructed. We demonstrated that the 5'-AAAAA-n5-GnCT-3' sequence is required for LcrF regulation and this motif is strictly located 4-bp upstream of a noncanonical promoter, in which the -35 and -10 elements are separated by a 21-bp spacer. Consistently, the putative binding motif was found in promoters of nine T3SS related operons or genes positively regulated by LcrF. Transcriptome analysis further confirmed that LcrF specifically activates T3SS genes in Yersinia. Collectively, our data suggest that LcrF has evolved to be a specific T3SS activator with a stringent sequence requirement for transcriptional regulation.

Protective effects of glucocorticoid on liver injury in a rat sepsis model.

Sepsis is one of the leading causes of death with unsatisfactory current treatments. The present study assessed the liver protective effect of glucocorticoids on different levels of inflammation in septic shock rats. A rat septic shock model was established by lipopolysaccharide (LPS) injection. Rats were divided into control (Control), high-inflammation treated with hydrocortisone (HT), high-inflammation non-treatment (HNT), low-inflammation treated with hydrocortisone (LT) and low-inflammation non-treatment (LNT) groups according to the levels of serum C-reactive protein (CRP), interleukin (IL)-6 and interferon (IFN)-γ. The mean arterial pressure and heart rate changes were continuously monitored and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured by an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining was performed to observe the pathological changes of liver tissue. Western blot analysis was used to detect the expression of p38 mitogen-activated protein kinase (MAPK) and NF-κB protein. The results demonstrated that following 7 days of treatment, there were no obvious differences in the serum CRP, IL-6 and IFN-γ levels between the HT group and the control group, whilst the HNT group, LT group and LNT group were significantly different compared with the HT and control groups. H&E staining demonstrated that the liver cells in the HT group were homogeneous following 7 days of treatment. Western blot analysis determined that the phosphorylation levels of p38MAPK and NF-κB in HT group were reduced significantly compared with the LT group, while there was no obvious difference with the control group after 7 days treatment. The present results indicated that glucocorticoids have better therapeutic effect on septic shock rats with high-inflammation compared with low-inflammation rats. The present study provides a novel approach for glucocorticoid treatment of septic shock.

XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial.

BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. RESULTS: The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in the oseltamivir group compared with 7 days (interquartile range 5-10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. CONCLUSIONS: Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .

Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial.

PURPOSE: To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP). METHODS: This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter. RESULTS: The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay. CONCLUSION: Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

A proteomic study on liver impairment in rat pups induced by maternal microcystin-LR exposure.

There is mounting evidence indicating that microcystins (MCs) are heptapeptide toxins. Recent studies have also shown that MCLR can transfer from mother to offspring, but it is unclear whether maternal MCLR can influence the liver of offspring or not. In this study, pregnant SD rats were injected intraperitoneally with a saline solution (control) or 10 µg/kg MCLR per day from gestational day 8 (GD8) to postnatal day 15 (PD15) for a total of 4 weeks. 2-DE and MALDI-TOF-TOF mass spectrometry were used to screen for MCLR target proteins in the livers of rat pups. Our results demonstrated that MCLR could accumulate in the livers of neonatal rats. Proteomics studies also showed that MCLR significantly influenced many proteins, including those involved in the cytoskeleton, metabolism and particularly oxidative stress. In addition, MCLR induced cellular structural damage and resulted in the production of intracellular reactive oxygen species (ROS) and lipid peroxidation. Moreover, protein phosphatase (PP) activity was inhibited and some serum biochemistry parameters were altered. These results suggest an early molecular mechanism behind the hepatotoxicity induced by maternal MC exposure and highlight the importance of monitoring MC concentrations in new-born mammals.

Silencing of poly(ADP-ribose) polymerase-1 suppresses hyperstretch-induced expression of inflammatory cytokines in vitro.

In addition to biochemical stimuli, physical forces also play a critical role in regulating the structure, function, and metabolism of the lung. Hyperstretch can induce the inflammatory responses in asthma, but the mechanism remains unclear. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that can regulate a variety of inflammatory cytokines expression. In the present study, we aimed to investigate the role and mechanism of PARP-1 in mechanical stretch-induced inflammation in human bronchial epithelial cells (HBEpiCs). HBEpiCs were simulated by mechanical stretch and cells under static were used as the control. PARP-1 expression was interfered by small interfering RNA. Oxidative stress was evaluated by DHE staining. DNA damage was assessed by comet assay. The results showed that interleukin-8 (IL-8) and vascular cell adhesion molecule-1 (VCAM-1) expression were regulated by hyperstretch in a time-dependent manner. Hyperstretch could increase PARP-1 expression and activity by inducing superoxide production and DNA damage. Silencing of PARP-1 attenuated hyperstretch-induced IL-8 and VCAM-1 up-regulation as well as monocytes adhesion, which were related to the inhibition of nuclear factor-kappa B (NF-κB) translocation. Our study showed that hyperstretch could induce inflammatory response and superoxide production as well as DNA damage in HBEpiCs. PARP-1 silencing decreased IL-8 and VCAM-1 expression, partly through inhibition of NF-κB translocation. PARP-1 played a fundamental role in hyperstretch-induced inflammation. PARP-1 silencing could be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.

Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome.

BACKGROUND: Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration (CVVH). Hence blood hemoperfusion with resin adsorption combined CVVH (HP+CVVH) has higher ability of mediator clearance, and can improve clinical outcomes in theory. This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration (HP+CVVH) on plasm cytokines like TNF-α, IL-1ß, IL-6, cellular immunity and prognosis in patients with multiple organ dysfunction syndrome (MODS). METHODS: This was a prospective, randomized clinical trial. A total of 30 patients who had been diagnosed with MODS were enrolled in this study. Patients were randomly allocated to routine treatment+HP+CVVH group (treatment group) and routine treatment+only CVVH group (control group). In the treatment group, patients received blood hemoperfusion with resin adsorption for 2 hours, and then received CVVH for 10 hours every day. In the control group, patients received CVVH for 12 hours only every day. The patients in the two groups received blood purification therapy for three days. The plasma of patients in the treatment group was obtained at 0, 2, 12, 24, 26, 36, 48, 50, 60 hours, 5th day, 7th day and 10th day, respectively. The plasma of patients in the control group was obtained at 0, 12, 24, 36, 48, 60 hours, 5th day, 7th day and 10th day, respectively. APACHE II score, T-lymphocytes subpopulations, blood lactate acid concentration, heart rate, breathing rate, and oxygenation index were observed. RESULTS: Plasma cytokines like TNF-α, IL-1ß, IL-6 decreased markedly after HP (P<0.01); T-lymphocytes subpopulations CD3+, CD4+, CD8+, CD4+/CD8+ increased after HP+CVVH or only CVVH. The plasma concentrations of TNF-α, IL-1ß and IL-6 in the two groups were not markedly different at 12, 36, and 50 hours. But on the 5th day, the plasma concentrations of TNF-α, IL-1ß and IL-6 in the treatment group were lower than those in the control group (P<0.05). On the 28th day, 5 patients died in the treatment group, and 6 patients in the control group. CONCLUSIONS: Both HP+CVVH and CVVH can clean plasma cytokines like TNF-α, IL-1ß, and IL-6, and improve cellular immunity and clinical symptoms and signs of patients. Compared with only CVVH, the plasma concentrations of TNF-α, IL-1ß and IL-6 were lower on the 5th day, and patients have an increased survival rate on the 28 day in the HP+CVVH group.