A novel Gd3+ DTPA-bisamide complex with high relaxivity as an MRI contrast agent.

A novel Gd(III) complex-based magnetic resonance imaging (MRI) contrast agent GdL has been designed and synthesized, which exhibited a much higher relaxivity (7.8 mM-1 s-1) than the commercially used Magnevist® (3.5 mM-1 s-1), good water solubility (>100 mg mL-1), excellent thermodynamic stability (log KGdL = 17.21 ± 0.27), high biosafety and biocompatibility. In particular, the relaxivity of GdL increased to 26.7 mM-1 s-1 in a 4.5% bovine serum albumin (BSA) solution at 1.5 T, which was not significant in other commercial MRI contrast agents. The interaction sites and interaction types of GdL and BSA were further demonstrated by molecular docking simulations. Furthermore, the in vivo MRI behaviour was evaluated by using a 4T1 tumour-bearing mouse model. These results suggested that GdL is an excellent T1-weighted MRI contrast agent and has the potential to be applied in clinical diagnosis.

Microfluidic-based modulation of triplet exciton decay in organic phosphorescent nanoparticles for size-assisted photodynamic antibacterial therapy.

The modulation of triplet exciton decay in organic room-temperature phosphorescence (RTP) materials has been considered as a promising strategy for highly efficient photodynamic therapy. In this study, we report an effective approach based on microfluidic technology to manipulate the triplet exciton decay for generating highly reactive oxygen species (ROS). BQD shows strong phosphorescence upon doping into crystalline BP, indicating the high generation of triplet excitons based on the host-guest interaction. Through microfluidic technology, BP/BQD doping materials can be precisely assembled to form uniform nanoparticles with no phosphorescence but strong ROS generation. The energy decay of the long-lived triplet excitons of BP/BQD nanoparticles emitting phosphorescence has been successfully manipulated via microfluidic technology to generate 20-fold enhanced ROS than that of BP/BQD nanoparticles prepared by nanoprecipitation. The in vitro antibacterial studies indicate that BP/BQD nanoparticles have high specificity against S. aureus microorganisms with a low minimum inhibition concentration (10-7 M). BP/BQD nanoparticles below 300 nm show size-assisted antibacterial activity, demonstrated using a newly developed biophysical model. This novel microfluidic platform provides an efficient approach to convert host-guest RTP materials into photodynamic antibacterial agents and to promote the development of antibacterial agents without cytotoxicity and drug-resistance issues based on the host-guest RTP systems.

Prediction of Severe Esophageal Varices in Patients With Cirrhosis Based on Levitt's CO Breath Test: A Proof of Concept Study.

GOALS: This study investigated the feasibility of using erythrocyte (RBC) lifespan determined by Levitt's CO breath test (LCOBT) to predict esophageal varices needing treatment (VNT) in patients with cirrhosis. BACKGROUND: Esophageal varix bleeding is a common fatal complication of cirrhosis and portal hypertension. The gold standard for identifying VNT is esophagogastroduodenoscopy (EGD), an invasive procedure with low patient compliance. VNT screening based on Baveno VI criteria has mediocre specificity. STUDY: RBC lifespan was determined by LCOBT in 53 cirrhotic patients (13 without varices, 11 mild/moderate varices, and 29 severe varices). Correlation of varix severity with RBC lifespan and other variables was analyzed. Rates of shortened RBC lifespan and thrombocytopenia (Baveno VI criteria) were compared. RESULTS: RBC lifespan correlated inversely with severity of varices ( r =-0.793, P <0.001). Mean RBC lifespans were 129±31, 96±21, and 59±21 days for Nonvarix, Mild/Moderate, and Severe groups. Shortened RBC lifespan (<75 d) was observed in 79.3% (23/29) of patients with severe varices, a frequency similar or identical to thrombocytopenia rates [original Baveno VI criteria, 86.2% (25/29), P =0.487; expanded criteria, 79.3% (23/29), P >0.999]. Among 24 patients without severe varices, shortened RBC lifespan was observed in 1 patient whereas thrombocytopenia was detected in 13 and 8 patients based on the original ( P <0.001) and expanded criteria ( P =0.010), respectively. CONCLUSIONS: RBC lifespan correlates inversely with varix severity in patients with cirrhosis. LCOBT may enable specific screening for VNT.

Levitt's CO breath test in the differential diagnosis of chronic isolated hyperbilirubinemia.

A key component of the differential diagnosis of isolated hyperbilirubinemia (HB) is distinguishing between hemolytic and non-hemolytic types. Routine hemolysis screening markers have unsatisfactory sensitivity and specificity. Erythrocyte (RBC) lifespan shortening, the gold standard marker of hemolysis, is seldomly measured due to the cumbersome and protracted nature of standard methods. A new Levitt's CO breath test method may enable simple, rapid RBC lifespan measurement. In this pilot prospective diagnostic study, Levitt's CO breath test was evaluated to discriminate hemolytic from non-hemolytic HB in adults. One hundred and thirty eligible non-smoking adult patients who were aged 18 or older, referred for chronic (>6 months) isolated HB or had a known diagnosis of isolated HB of a rare cause, were recruited, including 77 with non-hemolytic HB and 53 with hemolytic HB. ROC curve analysis was applied to determine the optimal cutoff for discriminating between hemolytic and non-hemolytic HB, and the performance was calculated. Results showed that the mean RBC lifespan in non-hemolytic HB (93 ± 26 d) was reduced (p= 0.001 vs. normal reference value of 126 d), but longer than that in hemolytic HB (36 ± 17 d;p= 0.001). RBC lifespans did not differ significantly between 26 patients with simple hemolytic HB (32 ± 14 d) and 27 patients with a Gilbert syndrome comorbidity (40 ± 18 d). ROC curve analysis revealed an optimal lifespan cutoff for discriminating between hemolytic and non-hemolytic HB of 60 d (AUC = 0.982), with a diagnostic accuracy of 95.4%, 94.3% sensitivity and 96.1% specificity respectively. These results indicate that Levitt's CO breath test seems to be very sensitive and specific for detecting hemolysis in adult patients with chronic isolated HB, and could enable simple, rapid, and reliable differential diagnosis of isolated HB. A large-scale validation study of the method is warranted.

Gilbert's syndrome coexisting with hereditary spherocytosis might not be rare: Six case reports.

BACKGROUND: Both Gilbert's syndrome (GS) and hereditary spherocytosis (HS) are common genetic disorders. However, comorbidity of GS with HS has always been considered a rare phenomenon, and it can impede accurate diagnoses in the presence of isolated unconjugated hyperbilirubinemia. CASE SUMMARY: In a study on Levitt's carbon monoxide (CO) breath test for the differential diagnosis of isolated hyperbilirubinemia, we found six GS patients with HS in 6 mo. The patients, including five males and one female, aged 25-58 years, were from four families and generally in good health. Their chronic fluctuating jaundice and/or hyperbilirubinemia had been diagnosed as simple constitutional jaundice for 6-30 years. Liver function tests showed isolated unconjugated hyperbilirubinemia with serum total bilirubin ranging from 20.7-75.4 µmol/L. Blood hemoglobin was normal in five cases, and slightly decreased in one (11.5 g/dL). Overt hemolytic signs were absent, while erythrocyte lifespan determined by the newly developed Levitt's CO breath test was significantly short (15-50 d), definitely demonstrating the presence of hemolysis. Given that their unconjugated hyperbilirubinemia compared inappropriately with hemolytic severity, as indicated by the hemoglobin level, further combined genetic tests for both UGT1A1 and hereditary erythrocyte deficiencies were conducted. These tests confirmed, at last, the coexistence of GS with HS. CONCLUSION: Comorbidity of GS and HS might not be uncommon in isolated unconjugated hyperbilirubinemia. While CO breath test would sensitively detect the hemolysis, the discordance between the hyperbilirubinemia and hemoglobin level could strongly indicate the coexistence of GS and HS.

Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction.

OBJECTIVE: Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking. METHODS: In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated. RESULTS: No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK. CONCLUSION: Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.

Solubility of Azilsartan in Methanol, Ethanol, Acetonitrile, n-Propanol, Isopropanol, Tetrahydrofuran, and Binary Solvent Mixtures between 293.15 and 333.15 K.

A precise determination method of azilsartan solubility between 293.15 and 333.15 K in several ordinary solvents and some of their aqueous mixtures was established by high-performance liquid chromatography. In all tested solvents, its solubility shows exponential growth with the increase in temperature. This trend is especially pronounced in methanol and ethanol. The order of solubility of azilsartan can be expressed as ethanol > tetrahydrofuran > ethanol/water (8/2, v/v) > methanol > methanol/water (8/2, v/v) > n-propanol > isopropanol > ethanol/Water (5/5, v/v) > acetonitrile. The solubility data of azilsartan were well correlated by the λh model. Moreover, the thermodynamic data including the dissolving enthalpy, entropy, and Gibbs free energy of azilsartan in each solvent were calculated which is crucial to its preparation technology study.

Carbon monoxide breath test assessment of mild hemolysis in Gilbert's syndrome.

BACKGROUND: Mild hemolysis is difficult to determinate by traditional methods, and its role in Gilbert's syndrome (GS) is unclear. The main aims were to inspect the erythrocyte (RBC) survival in GS by using Levitt's carbon monoxide (CO) breath test and to assess its contribution to unconjugated hyperbilirubinemia. METHODS: Fifty subjects with GS and 1 with type-II Crigler-Najjar syndrome (CN2) received RBC lifespan measurement with Levitt's CO breath test. Mean RBC lifespan was compared with normal referral value. Correlations of serum total bilirubin (TB) with RBC lifespan, blood panel data, demographic factors, and uridine diphosphate glucuronosyltransferase (UGT1A1) mutation load were calculated by Spearman analysis. Susceptibility factors for mild hemolysis were analyzed by multivariate regression analysis. RESULTS: The mean RBC lifespan of the GS subjects was significantly shorter than the normal reference value (95.4 ±â€Š28.9 days vs 126 days; t = -7.504, P < .01), with 30.0% below the lower limit of the normal reference range (75 days). The RBC lifespan of the participant with CN2 was 82 days. Serum TB correlated positively with UGT1A1 mutation load (γ = 0.281, P = .048), hemoglobin (γ = .359, P = .010) and hematocrit (γ = 0.365, P = .010), but negatively with RBC lifespan (γ = -0.336, P = .017). No significant susceptibility factors for mild hemolysis were found. CONCLUSIONS: The results indicate that mild hemolysis indeed, exists in a portion of patients with GS and might serve as an important contributor to unconjugated hyperbilirubinemia in addition to UGT1A1 polymorphism. Further studies on the mechanism and the potential risks in various medical treatments might be wanted.

Composition requirements of follow-up formula for 6-12-month-old infants: recommendations of a Chinese expert group.

BACKGROUND AND OBJECTIVES: The Chinese national standard of formula for 6-12-month-old infants (GB 10767- 2010) requires review and revision because it does not correspond to current scientific knowledge and data. The aim of this paper was to summarize the formula composition recommended for 6-12-month-old infants by a Chinese expert group. METHODS AND STUDY DESIGN: Formula composition recommendations for 6-12-month-old infants were devised by a Chinese expert group based on a detailed systematic review, which included nutrient intake, nutrient content of Chinese women's breast milk, and the latest adequate intake and tolerable upper intake levels, also referencing the Codex Alimentarius recommendations and those of other countries and considering the practice in products on the market. RESULTS: Compared with current standards, it was recommended that most compositional requirements be modified, including decreasing the maximum energy density from 85 to 75 kcal/100 mL, decreasing the protein content in milk-based formula from 2.9-5.0 g/100 kcal to 1.8-3.5 g/100 kcal, increasing the minimum content of lipids from 2.9 g/100 kcal to 3.5 g/100 kcal, providing the maximum amount of vitamins and minerals (including vitamin E, vitamin K, thiamin, riboflavin, vitamin B-6, vitamin B-12, niacin, folic acid, pantothenic acid, vitamin C, biotin, magnesium, calcium, phosphorus, and iodine), and changing the content of optional components such as taurine, docosahexaenoic acid, and arachidonic acid. CONCLUSIONS: These nutrient standard modifications based on recent evidence are expected to enhance feeding practices and further guarantee the health of 6-12-month-old infants in China.

Adjuvant Efficacy of Nutrition Support During Pulmonary Tuberculosis Treating Course: Systematic Review and Meta-analysis.

BACKGROUND: Malnutrition and tuberculosis (TB) tend to interact with each other. TB may lead to nutrition deficiencies that will conversely delay recovery by depressing immune functions. Nutrition support can promote recovery in the subject being treated for TB. The aim of this study was to evaluate the effectiveness of nutrition support on promoting the recovery of adult pulmonary TB patients with anti-TB drug therapy. METHODS: English database of the Cochrane Controlled Trials Register, PubMed, EMBASE, and Chinese database of CBM, CNKI, VIP, and WANFANG were searched. Randomized controlled trials comparing nutrition support (given for more than 2 weeks) with no nutrition intervention, nutrition advice only, or placebo-control for TB patients being anti-TB treated were included. Two reviewers conducted data extraction, assessed the quality of the studies independently, and any discrepancies were solved by the third reviewer. Data were entered and analyzed by RevMan 5.2 software, and meta-analysis was done using risk ratios (RR s) for dichotomous variables and mean differences (MDs) for continuous variables with 95% confidence intervals (CI s). RESULTS: A total of 19 studies (3681 participants) were included. In nutritional support for TB patients, pooled RR and its 95% CI of sputum smears- or culture-negative conversion rate and chest X-ray (CXR) absorption rate were 1.10 (1.04, 1.17) and 1.22 (1.08, 1.39), respectively, the pooled MD and its 95% CI of body mass index (BMI) and time of sputum smears or culture negativity were 0.59 (0.16, 1.2) and - 5.42 (-7.93, -2.92), respectively, compared with the control group. The differences in outcomes of CXR zone affected, TB score, serum albumin, and hemoglobin were not statistically significant (P = 0.76, 0.24, 0.28, and 0.20, respectively) between the intervention group and the control group. No systemic adverse events were recorded. CONCLUSIONS: During anti-TB course, nutrition support may be helpful in treatment of TB patients by improving both sputum smears- or culture-negative conversion rate and BMI, shortening the time of sputum conversion negative. Whether it can improve the final clinical effect, there still needs high-level quality studies to confirm in the future.