Adverse events reported in the included trials.

Adverse events reported in the included trials.</p

Methodological quality of the included studies.

Methodological quality of the included studies.</p

Characteristic of the included studies.

Characteristic of the included studies.</p

Intervention protocols of the included studies.

Intervention protocols of the included studies.</p

Flow diagram of included and excluded studies.

Flow diagram of included and excluded studies.</p

CRBSI per patient for trials that compared ethanol locks with heparin.

CRBSI per patient for trials that compared ethanol locks with heparin.</p

CRBSI per 1000 catheter days for trials that compared ethanol locks with heparin.

CRBSI per 1000 catheter days for trials that compared ethanol locks with heparin.</p

Table_1_Cox-LASSO Analysis for Hospital Mortality in Patients With Sepsis Received Continuous Renal Replacement Therapy: A MIMIC-III Database Study.XLSX

BackgroundSepsis remains the leading cause of mortality in-hospital in the intensive care unit (ICU). Continuous renal replacement therapy (CRRT) is recommended as an adjuvant therapy for hemodynamics management in patients with sepsis. The aim of this study was to develop an adaptive least absolute shrinkage and selection operator (LASSO) for the Cox regression model to predict the hospital mortality in patients with Sepsis-3.0 undergoing CRRT using Medical Information Martin Intensive Care (MIMIC)-III v1.4.MethodsPatients who met the Sepsis-3.0 definition were identified using the MIMIC-III v1.4. Among them, patients who received CRRT during ICU hospitalization were included in this study. According to the survival status, patients were split into death or survival group. Adaptive LASSO for the Cox regression model was constructed by STATA software. At last, nomogram and Kaplan-Meier curves were drawn to validate the model.ResultsA total of 181 patients who met Sepsis 3.0 criteria received CRRT were included in the study, in which, there were 31 deaths and 150 survivals during hospitalization, respectively. The overall in-hospital mortality was 17.1%. According to the results of multivariate Cox-LASSO regression analysis, use of vasopressor, international normalized ratio (INR) ≥1.5, and quick sequential organ failure assessment (qSOFA) score were associated with hospital mortality in patients with sepsis who underwent CRRT, but lactate level, mechanical ventilation (MV) support, PaO2/FiO2, platelet count, and indicators of acute kidney injury (AKI), such as blood urea nitrogen (BUN) and creatinine, were not independently associated with hospital mortality after adjusted by qSOFA. The risk nomogram and Kaplan-Meier curves verified that the use of vasopressor and INR ≥1.5 possess significant predictive value.ConclusionsUsing the Cox-LASSO regression model, use of vasopressor, INR ≥1.5, and qSOFA score are found to be associated with hospital mortality in patients with Sepsis-3.0 who received CRRT. This finding may assist clinicians in tailoring precise management and therapy for these patients who underwent CRRT.</p

Creation of Bioorthogonal Redox Systems Depending on Nicotinamide Flucytosine Dinucleotide

Many enzymes catalyzing biological redox chemistry depend on the omnipresent cofactor, nicotinamide adenine dinucleotide (NAD). NAD is also involved in various nonredox processes. It remains challenging to disconnect one particular NAD-dependent reaction from all others. Here we present a bioorthogonal system that catalyzes the oxidative decarboxylation of l-malate with a dedicated abiotic cofactor, nicotinamide flucytosine dinucleotide (NFCD). By screening the multisite saturated mutagenesis libraries of the NAD-dependent malic enzyme (ME), we identified the mutant ME-L310R/Q401C, which showed excellent activity with NFCD, yet marginal activity with NAD. We found that another synthetic cofactor, nicotinamide cytosine dinucleotide (NCD), also displayed similar activity with the ME mutants. Inspired by these observations, we mutated d-lactate dehydrogenase (DLDH) and malate dehydrogenase (MDH) to DLDH-V152R and MDH-L6R, respectively, and both mutants showed fully active with NFCD. When coupled with DLDH-V152R, ME-L310R/Q401C required only a catalytic amount of NFCD to convert l-malate. Our results opened the window to engineer bioorthogonal redox systems for a wide variety of applications in systems biology and synthetic biology

Flavonoids from the leaves of <i>Epimedium Koreanum</i> Nakai and their potential cytotoxic activities

Phytochemical studies on the leaves of Epimedium koreanum Nakai have resulted in the discovery of two new flavonol glycosides, koreanoside F (1) and koreanoside G (2), along with six known flavonoids. Their structures were elucidated on the basis of HRESIMS, UV, IR, 1 D NMR and 2 D NMR data. Absolute configurations of 1 and 2 was further determined by 13C-NMR spectra with gate decoupling (GD). All of the compounds were evaluated for cytotoxic activities by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay. The results indicated that compounds 3, 5, 6, 7 and 8 inhibited the proliferation of A549 and NCI-292 cells with IC50 values of 5.7–23.5 μM. Real-time monitoring in three kinds of lung cancer cells and a kind of human bronchial epithelial cells treated with compound 6 was also assessed.</p