In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Angelman syndrome (AS). METHODS: The proband with phenotypes suggestive of AS was subjected to copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and high-throughput next generation sequencing (NGS). Variant of the UBE3A gene was verified among family members by Sanger sequencing and bioinformatic analysis. RESULTS: NGS revealed that the proband has carried a heterozygous variant of the UBE3A gene, namely c.1517G>A (p.R506H). The variant has co-segregated with the disease in the pedigree. Multiple amino acid sequence alignment showed that the site of mutant residue is conserved among nine homologous species. The variant was predicted to be deleterious by bioinformatic analysis. CONCLUSION A novel variant of the UBE3A gene has been identified in a Chinese pedigree affected with AS. Above finding has further expanded the spectrum of UBE3A gene variants and phenotypes of AS, which also facilitated molecular diagnosis and genetic counseling for the family.
Angelman Syndrome/genetics* ; China ; DNA Copy Number Variations ; Humans ; Mutation ; Pedigree ; Phenotype

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

The mRNA-based vaccine technology is gradually developed as one of the new vaccine technologies in recent years. The technology is becoming more mature in terms of its stability and efficient delivery. Antigens encoded by mRNA vaccines are expressed in the cytoplasm and can induce the activation of both B cell responses and T cell cytotoxicity against infectious pathogens. In addition, the simple production process of synthetic mRNA vaccines can facilitate rapid response to emerging infectious diseases such as 2019-nCoV infection. In order to understand the current status of mRNA vaccine research and development for infectious diseases as well as providing reference for the development of clinically applicable mRNA vaccine against 2019-nCoV pandemic, this paper mainly reviewed the structural characteristics, advantages and challenges of mRNA vaccines and the current situation of vaccine research application in infectious diseases.

Objective:To explore the relationships between medical coping modes of patients with COVID-19 and general information and social supports.Methods:From January 28 to February 20, 2020, a total of 128 patients in a designated hospital in Wuhan with novel coronavirus pneumonia were investigated using the General Information Questionnaire and the Chinese version of the Medical Coping Modes Questionnaire (MCMQ) by convenient sampling. Pearson univariate analysis and multiple linear regression were used to analyze the relationship between the basic situation of patients with novel coronavirus pneumonia and coping modes.Results:The scores of the face dimension and avoidance dimension of patients with COVID-19 were lower than the norm model, while the yield dimension was higher than the norm model, and the differences were statistically significant ( P<0.05) . Support utilization and complexity were influencing factors of the face dimension ( P<0.05) . Support utilization and age were influencing factors of the yielding dimension ( P<0.01) . Subjective support, the complexity dimension of disease uncertainty and the number of confirmed patients in the family were influencing factors of the avoidance dimension ( P<0.01) . Conclusions:Patients with COVID-19 have poor medical coping modes, and they are prone to face the disease with a negative attitude. Patients are unwilling to face the disease and the tendency to yield to the disease is greater. And the older the patients, the less likely they are to succumb to the disease. The more patients diagnosed in the family, the less likely they are to avoid the disease. Patients with higher social supports and utilization have a more reasonable medical coping mode. This reminds medical staff to pay more attention to the psychological problems of patients in coping with COVID-19 and improve their coping modes and methods.

Objective To identify the role of phosphatidylinositol-3-kinase(PI3K) in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) and the involved mechanism.Methods Knockdown of p110α,receptor-interacting protein 1(RIP1) or both p110αand RIP1 was mediated by the specific short hairpin RNA (shRNA) lentivirus and verified by RT-PCR or Western blotting .In addition , Western blotting was used to detect phosphorylation of mixed lineage kinase domain-like protein(MLKL) and protein kinase B(AKT) or tetramerization of MLKL.Cell death was measured by micros-copy and flow cytometry.Results AKT phosphorylation and TNFα-induced necroptosis of L929 cells were suppressed by the inhibitors of PI3K or AKT, as well as p110αknockdown.Moreover, RIP1 knockdown did not inhibit L929 cell death induced by TNFαplus Z-VAD, but the RIP1-independent necroptosis was inhibited by p 110αknockdown.In addition, p110αknockdown suppressed MLKL phosphorylation and tetramerization induced by TNFαwith Z-VAD in L929 cells. Conclusion PI3K mediates necroptosis of L929 cells induced by TNFαby activating AKT and MLKL, respectively.

BACKGROUND: Because of the non-homology of protein and gene between human and animals, to promote osteogenesis or spinal fusion of animals by construction of tissue-engineered bone with the human gene has influenced the experimental validation.OBJECTIVE: To construct the seed cell line for bone tissue engineering with stable expression of human bone morphogenetic protein 2 (hBMP2).METHODS: The full-length hBMP2 gene was cloned from human muscle tissues by nested RT-PCR and transfected to human bone marrow mesenchymal stem cells (hBMSCs) with lipidosome. The transfected hBMSCs were cultured with G418 in vitro to screen and purify the cells. A series of analyses such as RT-PCR, dot-ELISA, immunohistochemstry and alkaline phosphatase activity analysis were performed to evaluate the situation of hBMP2 expression and secretion at 48 hours and 3 weeks after the transduction. hBMSCs transduced with empty plasmid and the normal hBMSCs served as positive control and blank control groups, respectively, which were used for observation of cell growth, proliferation and biological characteristics of transfected cells. RESULTS AND CONCLUSION: The transfected hBMSCs appeared in small groups or clusters, and had a good proliferation after subculture in vitro. Some G418-resistance cell clones and calcium nodules were found when cultured with G418 in vitro. No significant difference was noted in the cell proliferation between the hBMP2 transfection group and two control groups. The ALP activity in the hBMP2 transfection group remained significantly higher than that in the two control groups (P < 0.01). At 48 hours and 3 weeks after transduction, hBMSCs could express actively hBMP2 by RT-PCR monitoring, and had a positive reaction of dot-ELISA and immunohistochemical analysis. The expression of hBMP2 gene in the experiment group at 48 hours was significantly higher than that at 3 weeks after transduction while there was no expression of hBMP2 gene in the two control groups. The above results show that the hBMSCs transfected by hBMP2 gene not only have potentials of normal proliferation and osteogenic differentiation, but also can stably express hBMP2.

OBJECTIVETo analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane.

METHODThis was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used.

RESULTTotally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313).

CONCLUSIONCompared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.

Basement Membrane ; pathology ; Child ; Collagen Type IV ; genetics ; DNA Mutational Analysis ; Deafness ; Humans ; Kidney Failure, Chronic ; Male ; Mutation, Missense ; Nephritis, Hereditary ; genetics ; pathology ; Proteinuria ; Retrospective Studies