1.Pathogenicity and Transcriptomic Profiling Revealed Activation of Apoptosis and Pyroptosis in Brain of Mice Infected with the Beta Variant of SARS-CoV-2.
Han LI ; Bao Ying HUANG ; Gao Qian ZHANG ; Fei YE ; Li ZHAO ; Wei Bang HUO ; Zhong Xian ZHANG ; Wen WANG ; Wen Ling WANG ; Xiao Ling SHEN ; Chang Cheng WU ; Wen Jie TAN
Biomedical and Environmental Sciences 2025;38(9):1082-1094
OBJECTIVE:
Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351).
METHODS:
K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.
RESULTS:
Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.
CONCLUSION
These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals
;
COVID-19/genetics*
;
Mice
;
Brain/metabolism*
;
Apoptosis
;
Mice, Inbred C57BL
;
SARS-CoV-2/physiology*
;
Pyroptosis
;
Gene Expression Profiling
;
Transcriptome
;
Male
;
Female
2.Construction of multi-dimensional value evaluation index system of intraocular lens
Bao-Ying TAN ; Ai-Ling LIN ; Huang-Ying SUN ; Xin PENG ; Chuan-Chao LUO ; Jian-Wei XUAN
Chinese Medical Equipment Journal 2023;44(11):83-89
Objective To develop two multi-dimensional value evaluation index systems for intraocular lens(IOL)to assist decision makers in selecting appropriate IOLs.Methods IOL value assessment indexes were determined preliminarily through literature research and expert consultation,and the weights of the indexes were calculated through hierarchical analysis method and then ranked to form two evaluation index systems.Results Two multi-dimensional value evaluation index systems were constructed for monofocal and refractive IOLs respectively,which both contained 3 first-level indicators and 13 second-level indicators;the evaluation index system for monofocal IOL involved in 26 third-level indicators,and the other for refractive IOL had 33 third-level indicators.The three first-level indicators of the two systems were ranked by weight as clinical dimension,economic dimension and institutional dimension.The monofocal IOL evaluation index system had product performance being the second-level indicator with the highest weight,and the top three third-level indicators with the highest weights being lens capsule biocompatibility,risk of intraocular lens damage during implantation and range of applicable populations;the refractive IOL evaluation index system had clinical efficacy(vision)being the second-level indicator with the highest weight,and the top three third-level indicators with the highest weights being distant vision,(astigmatism)rotational stability/postoperative axial rotation and near vision.Conclusion The multi-dimensional value evaluation index systems developed provide references for comprehensive value evaluation of IOLs.[Chinese Medical Equipment Journal,2023,44(11):83-89]
3.Research on the present situation of detection strategies for infectious markers related to transfusion transimission in China
Wei TAN ; Shengyan YING ; Ning CHENG ; Yujun LI ; Xiaoli CHEN ; Fang WANG ; Yang ZHANG ; Xiaojie LIU ; Lin BAO ; Yong DUAN ; Chen MA ; Chunlan LIU ; Dengfeng WANG ; Zhijun ZHEN ; Li LI ; Jian ZHANG ; Ranran LU ; Peng WANG ; Mingxia LI ; Xinli JIN ; Xiaobo CAI ; Mei YU ; Jianling ZHONG ; Lili ZHU ; Jianping LI
Chinese Journal of Experimental and Clinical Virology 2023;37(4):383-388
Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.
4.Protective Mechanism of Lavender Against Skin Photodamage Based on Network Pharmacology and Experimental Verification
Ya YANG ; Hai-yan BAO ; Ying-ying KANG ; Rong-chang LIU ; Mao-jie ZHOU ; Wei TAN ; Zheng-yi GU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):167-174
ObjectiveTo predict the active ingredients and mechanism of action of lavender in protecting skin photodamage based on network pharmacology and molecular docking technology,and further verify possible signal pathways via animal experiments. MethodThe active ingredients and potential targets of lavender were obtained by SwissTargetPrediction,PharmMapper, and literature. Skin photodamage-related targets were searched from GeneCards,Online Mendelian Inheritance in Man (OMIM),DrugBank and DisGeNET databases. After common targets of the two were screened out,STRING was adopted to analyze the protein-protein interaction (PPI) network,where topological analysis and core target screening were performed by CytoNCA plug-in of Cytoscape 3.8.2. Based on DAVID, gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out among the intersection targets, and the active ingredients of lavender and the signal pathway proteins were selected and verified via molecular docking with AutoDock vina 1.1.2. Finally, mouse photodamage model was established by UVB irradiating the bare skin of mouse back, and the skin condition was observed by naked eyes. Hematoxylin-eosin (HE) and picric acid-acid fuchsin staining (Van Gieson, VG) were used to observe the pathological changes of mouse skin tissues. Western blot was employed to detect the protein expression in mouse skin tissues to further validate the key signal pathways. ResultIn this study,6 active ingredients of lavender,526 potential targets,2 688 disease-related targets,and 258 intersection targets were screened out, and 16 core targets were obtained by PPI network. Additionally, 113 related signal pathways were obtained by KEGG pathway analysis,among which phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway and nuclear transcription factor-κB (NF-κB) signal pathway might play a key role in skin photodamage protection by lavender. Molecular docking showed that the active ingredients and the signal pathway proteins were well docked. Animal experiments indicated that the total flavonoids of lavender improved the appearance and histopathological condition of mouse skin, reduced the relative expression levels of phosphorylated(p)-PI3K,p-Akt,and B cell lymphoma 2 (Bcl-2) proteins (P<0.05,P<0.01), and increased relative expression level of Bcl-2-associated X protein(Bax) (P<0.05). ConclusionLavender exerts synergistic effect in resisting skin photodamage,with the characteristics of multi-components,multi-targets,and multi-pathways, which provides a basis for subsequent in-depth research on the complex mechanism of lavender against skin photodamage.
5.Mycena subpiligera sp. nov., a Symbiotic Species from China Associated with the Seed Germination of Gastrodia elata
Li-na LIU ; Guo-ying ZHOU ; Ai-rong SHEN ; Bao-ming SHEN ; Yun TAN ; Zhu-ming TAN
Mycobiology 2022;50(5):294-301
Mycena subpiligera, a new taxon in sect. Fragilipedes that can strongly enhance the germination efficiency of Gastrodia elata seeds, was discovered in subtropical areas of China. As revealed by a morphological comparison with related Mycena species as well as maximum likelihood (ML) and Bayesian phylogenetic analyses based on sequences of the internal transcribed spacer (ITS) and the large subunit (LSU) regions of nuclear ribosomal RNA, the new taxon can be distinguished from phenotypically similar and phylogenetically related species. Optimal cultural conditions for M. subpiligera basidiomata are reported, and the germination rate of the new species is compared with that of M. citrinomarginata.
6.Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.
Hong-Xing PAN ; Jian-Kai LIU ; Bao-Ying HUANG ; Gui-Fan LI ; Xian-Yun CHANG ; Ya-Fei LIU ; Wen-Ling WANG ; Kai CHU ; Jia-Lei HU ; Jing-Xin LI ; Dan-Dan ZHU ; Jing-Liang WU ; Xiao-Yu XU ; Li ZHANG ; Meng WANG ; Wen-Jie TAN ; Wei-Jin HUANG ; Feng-Cai ZHU
Chinese Medical Journal 2021;134(11):1289-1298
BACKGROUND:
The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.
METHODS:
Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.
RESULTS:
In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.
CONCLUSIONS:
Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.
TRIAL REGISTRATION
http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult
;
COVID-19
;
COVID-19 Vaccines
;
Double-Blind Method
;
Humans
;
SARS-CoV-2
;
Vaccines, Inactivated/adverse effects*
7.Full-Length Genome Sequencing of SARS-CoV-2 Directly from Clinical and Environmental Samples Based on the Multiplex Polymerase Chain Reaction Method.
Pei Hua NIU ; Xiang ZHAO ; Rou Jian LU ; Li ZHAO ; Bao Ying HUANG ; Fei YE ; Da Yan WANG ; Wen Jie TAN
Biomedical and Environmental Sciences 2021;34(9):725-728
8.Integrating Physical Activity into School-based Eye Health Services: A Policy and Development Study
Sheng ZHOU ; Meng ZHANG ; Zhuo-ying QIU ; Guo-xiang WANG ; Fu-bing QIU ; Jian YANG ; Shao-pu WANG ; Ting ZHU ; An-qiao LI ; Chuan-ping HAO ; Rong-bin YIN ; Qiang TAN ; Geng CAI ; Xiu-qi TANG ; Jing LIU ; Bao-yi YANG
Chinese Journal of Rehabilitation Theory and Practice 2021;27(12):1374-1383
Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.
9.Real-time reverse transcription-polymerase chain reaction assay panel for the detection of severe acute respiratory syndrome coronavirus 2 and its variants.
Rou-Jian LU ; Li ZHAO ; Bao-Ying HUANG ; Fei YE ; Wen-Ling WANG ; Wen-Jie TAN
Chinese Medical Journal 2021;134(17):2048-2053
BACKGROUND:
With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time.
METHODS:
We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7).
RESULTS:
Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively.
CONCLUSIONS
Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.
COVID-19
;
Humans
;
RNA, Viral/genetics*
;
Real-Time Polymerase Chain Reaction
;
Reverse Transcription
;
SARS-CoV-2
;
Sensitivity and Specificity
10.Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology.
Yan-Yan ZHOU ; Wen-Ya GAO ; Xin-Ru GU ; Zhou-Quan CHEN ; Hai-Yu ZHAO ; Bao-Lin BIAN ; Li-Xin YANG ; Nan SI ; Hong-Jie WANG ; Ying TAN
China Journal of Chinese Materia Medica 2020;45(13):3035-3044
UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 μm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.
Chromatography, High Pressure Liquid
;
Coumarins
;
analysis
;
Drugs, Chinese Herbal
;
Flavonoids
;
analysis
;
Mass Spectrometry

Result Analysis
Print
Save
E-mail