Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis.

We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.

A terminal alkyne and disulfide functionalized agarose resin specifically enriches azidohomoalanine labeled nascent proteins.

Nascent proteome presents dynamic changes in response to a certain stimulus. Thus, monitoring nascent proteome is critical to uncovering the involved biological mechanism. But the low-abundance of nascent proteome against an overwhelming pre-existing proteome limits its identification and quantification. Herein, we present a novel strategy to enrich nascent proteome from whole cell lysate for further analysis by mass spectrometry. We employed a terminal alkyne and disulfide functionalized agarose resin to capture nascent proteome which had been labeled by L-azidohomoalanine. Results from the western blot, silver staining and pulse metabolic labeling suggested that the nascent proteome could be enriched efficiently. Applied to Hela cells, the method identified about 700 nascent proteins with good correlation with previous reports. The above indicates that our strategy can be used to reveal the proteome dynamics of biological processes.

BirA*-protein A fusion protein based BioEnhancer amplifies western blot immunosignal.

Western blot (protein immunoblot) is a widely used analytical technique in molecular biology. Utilizing the specific recognizing primary antibody, proteins immobilized on various matrix are investigated by subsequent visualization steps, for example, by the horse radish peroxidase conjugated secondary antibody incubation. Methods to improve the sensitivity in protein identification or quantification are appreciated by biochemists. Herein, we report a new strategy to amplify Western blot signals by constructing a probe with proximal labeling and IgG targeting abilities. The R118G mutation attenuated the biotin-AMP binding affinity of the bacterial biotin ligase BirA*, offering a proximity-dependent labeling ability, which could be used as a signal amplifier. We built a BirA*-protein A fusion protein (BioEnhancer) that specifically binds to IgG and adds biotin tags to its proximal amine groups, enhancing the immunosignal of target proteins. In our experiments, the BioEnhancer system amplified the immunosignal by tenfold compared to the standard western blot. Additionally, our strategy could couple with other signal enhancement methods to further increase the western blot sensitivity.

Good's buffers have various affinities to gold nanoparticles regulating fluorescent and colorimetric DNA sensing.

Citrate-capped gold nanoparticles (AuNPs) are highly important for sensing, drug delivery, and materials design. Many of their reactions take place in various buffers such as phosphate and Good's buffers. The effect of buffer on the surface properties of AuNPs is critical, yet this topic has not been systematically explored. Herein, we used halides such as fluoride, chloride, and bromide as probes to measure the relative adsorption strength of six common buffers. Among them, HEPES had the highest adsorption affinity, while MES, citrate and phosphate were weakly adsorbed with an overall ranking of HEPES > PIPES > MOPS > MES > citrate, phosphate. The adsorption strength was reflected from the inhibited adsorption of DNA and from the displacement of pre-adsorbed DNA. This conclusion is also supported by surface enhanced Raman spectroscopy. Furthermore, some buffer molecules did not get adsorbed instantaneously, and the MOPS buffer took up to 1 h to reach equilibrium. Finally, a classic label-free AuNP-based colorimetric sensor was tested. Its sensitivity increased by 15.7-fold when performed in a MES buffer compared to a HEPES buffer. This study has articulated the importance of buffer for AuNP-based studies and how it can improve sensors and yield more reproducible experimental systems.

The effect of phospho-peptide on the stability of gold nanoparticles and drug delivery.

BACKGROUND: Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. RESULTS: Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. CONCLUSION: In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy.

Fetal Lymphangioma: Prenatal diagnosis on ultrasound, treatment, and prognosis.

OBJECTIVE: To investigate the characteristics of fetal lymphangioma, including their location, imaging features, prenatal and differential diagnoses, treatment, and prognosis. STUDY DESIGN: Imaging data of 79 patients with fetal lymphangioma treated at our hospital were obtained. Imaging modalities included prenatal and post-natal magnetic resonance imaging (MRI), prenatal and post-natal color Doppler ultrasound, and post-natal contrast-enhanced computed tomography (CT). Modalities of delivery and treatment were selected according to the location and size of lymphangioma. RESULTS: Among the 133,322 fetuses of 130,202 pregnant women examined at our hospital, 5 fetuses were misdiagnosed and the diagnosis was missed in 5 fetuses prenatally. Finally, 79 had lymphangioma, confirmed by ultrasound, MRI, post-natal CT, and pathological results obtained postoperatively or on autopsy. The diagnostic coincidence rate of lymphangioma was 88.1% (74/84 cases). Of the 79 fetuses with a lymphangioma, septation of the mass was identified in 66 cases (83.54%), with no evidence of septation in the remaining 13 fetuses (16.46%). With regard to location, the lymphangioma was located in the neck in 50 fetuses (63.29%). Interventional sclerotherapy, using bleomycin, was performed in 22 neonates, of which 3 underwent ex utero intrapartum treatment (EXIT) due to evidence of airway or esophageal obstruction (16 patients underwent expectant management; 7 surgical operation). Thirty-two fetuses underwent medical termination and 2 fetuses died in-utero. Of the 16 patients who had expectant treatment, the lesions retroregressed during the intra-uterine period in 7 fetuses, before the post-natal age of 6 months in 4 neonates, and before the age of 2 years in 3 neonates. Of the 7 neonates who were treated surgically, relapse occurred in 1 case, which required re-operation. CONCLUSIONS: Prenatal ultrasound provides a clear differential diagnosis of fetal lymphangioma. Interventional therapy should be the first-choice treatment for neonates with a lymphangioma confirmed postnatally.