COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.
Mice ; Animals ; Colitis, Ulcerative/metabolism* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Metabolomics ; Colon ; Disease Models, Animal ; Biomarkers ; Dextran Sulfate/therapeutic use*

Humans ; Multiple Myeloma/drug therapy* ; Feasibility Studies ; Antibodies, Monoclonal/adverse effects* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.

This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.
Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Gas Chromatography-Mass Spectrometry ; Reproducibility of Results ; Drugs, Chinese Herbal/chemistry*

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.
Humans ; Infant ; Gene Expression Profiling ; Sudden Infant Death/genetics* ; Gene Regulatory Networks ; Protein Interaction Maps/genetics* ; Computational Biology

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective To compare the effectiveness of loop-mediated isothermal amplification (LAMP) assay and microscopic examinations for detection of Schistosoma japonicum infections in Oncomelania hupensis in transmission-interrupted regions, so as to provide insights into the optimization of snail surveillance tools in these regions. Methods Four hilly schistosomiasis-endemic villages where transmission interruption was achieved were selected in Heqing County of Yunnan Province as the study villages, including Xinzhuang and Gule villages in hilly regions and Lianyi and Yitou villages in dam regions. Snail survey was performed by means of systematic sampling combined with environmental sampling in July 2018. All captured snails were identified for S. japonicum infections using microscopy. In addition, 10 to 20 snails were randomly sampled from each snail habitat following microscopy, numbered according to environments and subjected to LAMP assay. The positive rate of settings with S. japonicum-infected snails was compared among villages. Results A total of 7 949 living snails were captured from 83 snail habitats in 4 villages, and no S. japonicum infection was detected in snails. There were 226 mixed samples containing 1 786 snails subjected to LAMP assay, and positive LAMP assay was found in 3 mixed samples from 3 snail habitats in 2 dam villages. The positive rates of settings with S. japonicum-infected snails were comparable between Lianyi Village (one setting) and Yitou Village (2 set tings) (5.89% vs. 14.29%, P = 0.344). However, the overall positive rate of settings with S. japonicum-infected snails was significantly higher in dam villages (9.67%, 3/31) than in hilly villages (0) (P = 0.048). Conclusions LAMP assay is more sensitive to detect S. japonicum infections in O. hupensis than conventional microcopy method, which may serve as a supplementary method for detection of S. japonicum infections in O. hupensis in high-risk snail habitats in hilly transmission-interrupted regions.

Objective To study stress distributions of the cartilage around the hip joint in stress environment of complete gait cycle, and explore the optimal correction angle of bone block in curved periacetabular osteotomy (CPO), so as to provide theoretical references for clinical operation. Methods Based on CT scans from a healthy volunteer and a patient with development dysplasia of hip (DDH), the three-dimensional (3D) model including pelvis and proximal femur was reconstructed. The cortical bone and cancellous bone were distinguished by dividing the masks, and the material attributes were assigned to the finite element model. A total of 100 different postoperative models were obtained by simulating CPO in DDH model, by adjusting lateral center edge angle (LCEA) and anterior center edge angle (ACEA). According to hip joint stresses in complete gait cycle, the model was loaded respectively, and stress changes of normal, preoperative and postoperative acetabular cartilage were analyzed and compared. ResultsThe minimum peak contact stresses of acetabular cartilage of DDH patient at heel landing phase, start phase of single leg support, mid phase of single leg support, end phase of single leg support and double support phase after simulated CPO operation were 5.273, 6.128, 7.463, 6.347, 6.582 MPa, which were decreased by 2.159, 2.724, 2.249, 2.164, 2.119 MPa,respectively, compared with those before operation. The contact area between femoral head and acetabulum was significantly increased after operation, but it was still smaller than that of normal volunteers. Conclusions The optimal correction angle of LCEA and ACEA can be obtained by using finite element method, and the simulation of CPO surgery on different patients is of great significance to improve surgical accuracy and efficiency.

CRISPR-Cas9 gene editing technology has been widely used in Saccharomyces cerevisiae.However, the effects of Cas9, as an exogenous protein, on the growth and production of natural products in S.cerevisiae are still unclear.In this study, Cas9 gene was expressed in S.cerevisiae by integration into the genome and construction into vectors, and two natural products, carotenoid and miltiradiene, were selected as the target products to study the effects of Cas9 expression on yeast growth and production capacity.The results showed that whether Cas9 was integrated into the genome or expressed by vectors, Cas9 inhibited the growth of S.cerevisiae, which was more obvious in the form of genome integration.When Cas9 was integrated into the genome, it had no effect on the production of carotenoid and miltiradiene by S.cerevisiae, but when Cas9 was expressed by vectors, the ability of S.cerevisiae to produce carotenoids and miltiradiene was significantly reduced.Therefore, in order to further efficiently knock out Cas9 after gene editing and minimize the adverse impact of Ura3 and Trp1 vectors, this study systematically explored the removal efficiency of the two vectors, and a plasmid capable of efficient gene editing was constructed, which optimized the application of CRISPR-Cas9 gene editing system in S.cerevisiae, and provided reference for the application of gene editing technology based on Cas9.
Biological Products ; CRISPR-Cas Systems ; Carotenoids/metabolism* ; Gene Editing/methods* ; Saccharomyces cerevisiae/metabolism*