The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective:To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames.Methods:Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ2 test. Results:NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m 2, respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) μmol/L, (346.57 ± 89.49) μmol/L, and (344.89 ±89.67) μmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) μmol/L, 73.0 (65.0, 83.5) μmol/L, and 73.0 (65.0, 83.0) μmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences ( P<0.05). Conclusion:Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

Objective:To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies.Methods:Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA).Results:A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR=0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR=0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR=0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary ( Z=3.29). Conclusion:Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Objective:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Liver fibrosis is the leading cause of the morbidity and mortality of liver diseases worldwide and has become one of the key issues in the research on chronic liver diseases among domestic and foreign scholars. An increasing amount of evidence has shown that gut microbiota dysbiosis plays a crucial role in the development and progression of liver fibrosis, and improvement of gut microbiota dysbiosis has become a new target for anti-fibrotic treatment. At present, traditional Chinese medicine has attracted much attention in improving gut microbiota. Studies have shown that "harmonizing liver and spleen" plays an important role in reducing fibrosis degree and delaying the progression of liver fibrosis. Therefore, based on the theory of "harmonizing liver and spleen", the achievements in liver-gut axis and gut microbiota by modern molecular biological techniques can provide a theoretical basis for the treatment of liver fibrosis from "harmonizing liver and spleen" in clinical practice, as well as new directions and ideas for anti-fibrotic treatment with traditional Chinese medicine.

Alternative splicing (AS) is a process by which the transcriptome diversity, and thereby the proteome diversity, is augment-ed by splicing or joining together different parts of the pre-mRNA in eukaryotic cells . AS at different splice sites is regulated by multi-ple cis-acting elements and trans-acting factors. Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease in which there is a translocation between the long arms of chromosome 9 and chromosome 22, represented as t(9;22) (q34;q11). This translocation results in the formation of a BCR-ABL fusion gene. Hence it is not surprising that resistance to tyrosine kinase inhibitors, which inhibit BCR-ABL activity, has become a critical problem in the clinical treatment of CML. Using second generation high-throughput sequencing technology, it has been found that AS abnormalities are closely related to the occurrence, progression, drug resistance, and immune escape of CML. This paper reviews the research related to AS and CML resistance and investigates the potential causes of CML resis-tance. Drug resistance mechanisms and potential therapeutic targets are also reviewed.