[Early effect of extracorporeal membrane oxygenation and factors related to early outcome in adult patients with fulminant myocarditis].

Objective: To evaluate the efficacy within the first 24 h post extracorporeal membrane pulmonary oxygenation (ECMO) and the impact of early efficacy on the prognosis of adult patients with fulminant myocarditis (FM). Methods: This retrospective case analysis study included hospitalized patients (age≥18 years) who were diagnosed with fulminant myocarditis from November 2016 to May 2021 in the First Affiliated Hospital of Zhengzhou University. Patients were divided into survival or non-survival groups according to treatment outcomes. The age, sex, treatments, drug use, ECMO use, clinical and laboratory data (before and 24 h after the use of ECMO) were analyzed. The change rate of clinical and laboratory data after 24 h use of ECMO was calculated to find differences between two groups. Multivariate logistic regression was used to analyze the related factors with in-hospital death and complication between the two groups. Results: A total of 38 FM patients treated with ECMO were included. There were 23 cases (60.5%) in the survival group, aged (39.6±13.7) years, and 17 (73.9%) cases were female. The total ECMO time was (134.4±71.3)h. There were 15 cases (39.5%) in non-survival group, aged (40.0±15.8) years, and there were 12(80.0%) female, the ECMO time was (120.1±72.4) h in this group. The proportion of tracheal intubation and continuous renal replacement therapy in the survivor group and dosage of norepinephrine within 24 h after ECMO implantation were significantly less than in non-survival group (all P<0.05). There was no significant difference in all efficacy related biochemical indexes between two groups before ECMO use. The levels of lactic acid, procalcitonin, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase-MB, cardiac troponin I and N-terminal B-type natriuretic peptide prosoma were significantly less in survival group than in non-survival group at 24 h after the use of ECMO (all P<0.05). Results of multivariate logistic regression analysis showed that the higher 24 h change rate of creatinine (OR=0.587, 95%CI 0.349-0.986, P=0.044) and creatine kinase-MB (OR=0.177, 95%CI 0.037-0.841, P=0.029) were positively correlated with reduced risk of in-hospital mortality. The central hemorrhage and acute kidney injury in survival group were less than in non-survivor group (P<0.05). Conclusions: After 24 h early use of ECMO in FM patients, the improvement of various efficacy related biochemical test indexes in the survival group was better than that in the non-survival group. Faster reduction of creatine kinase-MB and creatinine values within 24 h ECMO use is positively correlated with reduced risk of in-hospital mortality in adult patients with FM.

293FT is a highly suitable mammalian cell line for the in vitro enzymatic activity analysis of typical P450 proteins.

Mammalian cells have been widely used for the in vitro evaluation of the functional effect of allelic variants of cytochrome P450 (CYP). The aim of this study was to determine the most suitable mammalian cell line for the in vitro drug metabolism analysis of CYP variants. Three reported cell lines (COS-7, HepG2, 293T) and one fast-growing variant of the 293 cell line 293FT were transfected with vectors expressing green fluorescent protein or typical variants of CYP2C9, CYP2C19 or CYP2D6 to investigate the protein expression levels and the catalytic activity of expressed CYP allelic variants. The transfected 293FT cells had the highest protein expression level and exhibited the highest enzymatic activity, while HepG2 cells showed the lowest activity among the four tested cell lines. Simultaneously, 293FT cells still maintained the similar relative enzymatic ratio among three typical CYP2C9 variants to that of the commonly used COS-7 cells. In addition, 293FT cells could also be used for the in vitro functional evaluation of two other typical P450 proteins, CYP2C19 and CYP2D6. Therefore, the 293FT cell line is more suitable for the in vitro enzymatic activity analysis of typical P450 proteins than any other reported mammalian cell lines.

Identification of a new non-synonymous mutation in HLA-B gene, HLA-B*15:320, in a Chinese individual by sequence-based typing.

The novel allele HLA-B*15:320 differs from HLA-B*15:01:01:01 at position 709 in exon 4 (A>T, Ile>Phe).

A linewidth-narrowed and frequency-stabilized dye laser for application in laser cooling of molecules.

We demonstrate a robust and versatile solution for locking the continuous-wave dye laser for applications in laser cooling of molecules which need linewidth-narrowed and frequency-stabilized lasers. The dye laser is first stabilized with respect to a reference cavity by Pound-Drever-Hall (PDH) technique which results in a single frequency with the linewidth 200 kHz and short-term stabilization, by stabilizing the length of the reference cavity to a stabilized helium-neon laser we simultaneously transfer the ± 2 MHz absolute frequency stability of the helium-neon laser to the dye laser with long-term stabilization. This allows the dye laser to be frequency chirped with the maximum 60 GHz scan range while its frequency remains locked. It also offers the advantages of locking at arbitrary dye laser frequencies, having a larger locking capture range and frequency scanning range to be implemented via software. This laser has been developed for the purpose of laser cooling a molecular magnesium fluoride beam.

A new HLA-A*24 allele, HLA-A*24:02:87, identified by sequencing-based typing in a Chinese volunteer bone marrow donor.

Novel allele HLA-A*24:02:87 has one nucleotide change with A*24:02:01:01 in exon 3 at position 594 C>T.

CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database.

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n=1127) and Hebei (n=1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.

Lowered Nudix type 5 expression leads to cellular senescence in IMR-90 fibroblast cells.

The molecule 8-oxo-7,8-dihydroguanine (8-oxoGua), an oxidized form of guanine, can pair with adenine or cytosine during nucleic acid synthesis. RNA sequences that contain 8-oxoGua cause translational errors that lead to the synthesis of abnormal proteins. Human Nudix type 5 (NUDT5), a MutT-related protein, catalyzes the hydrolysis of 8-oxoGDP to 8-oxoGMP, thereby preventing the misincorporation of 8-oxoGua into RNA. To investigate the biological roles of NUDT5 in human fibroblast cells, we established cell lines with decreased levels of NUDT5 expression. In NUDT5 knockdown cells, the RNA oxidation levels were significantly higher, the rates of cellular senescence and cell apoptosis were significantly increased, and the cell viability was significantly decreased in comparison with control cells. These results suggested that the NUDT5 protein could play significant roles in the prevention of RNA oxidation and survival in human fibroblast cells.