1.Analysis of T7 RNA Polymerase: From Structure-function Relationship to dsRNA Challenge and Biotechnological Applications
Wei-Chen NING ; Yu HUA ; Hui-Ling YOU ; Qiu-Shi LI ; Yao WU ; Yun-Long LIU ; Zhen-Xin HU
Progress in Biochemistry and Biophysics 2025;52(9):2280-2294
T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.
2.Relationship between Helicobacter pylori infection and disease severity and pathological type of inpatients with intestinal polyps
Wei YOU ; Dalin LU ; Yan CHEN ; Xin WANG ; Yizheng FANG ; Lunshan WANG
Journal of Public Health and Preventive Medicine 2025;36(5):85-88
Objective To investigate the relationship between Helicobacter pylori (Hp) infection and disease severity and pathological type of intestinal polyps in inpatients. Methods The data of 303 inpatients with intestinal polyps in the hospital from August 2022 to February 2025 were collected and analyzed. The clinical characteristics of patients were analyzed, and the influencing factors of pathological types of polyps were explored. Results Among the 303 inpatients with intestinal polyps, there were 135 Hp positive cases and 168 Hp negative cases. The number of polyps, maximum polyp diameter, number of ileocecus/ascending colon/transverse colon polyps, number of descending colon/sigmoid colon/rectal polyps and adenomatous polyps in the Hp-positive group were higher than those in the Hp-negative group (P<0.05). Multivariate logistic regression analysis indicated that age [OR (95%CI)=1.03 (1.01-1.05)] and positive Hp[OR (95%CI)=2.61 (1.62-4.20)] were independent risk factors of occurrence of adenomatous polyps (P<0.05). ROC curve results revealed that the AUCs of age, positive HP and combination in the diagnosis of adenomatous polyps were 0.574, 0.608 and 0.646, and the 95%CI values were 0.509-0.638, 0.545-0.672 and 0.584-0.708 respectively. The efficiency of combination of the two indexes was higher than that of single diagnosis. Conclusion Hp infection is associated with disease severity in inpatients with intestinal polyps, and it may be involved in the occurrence and development of adenomatous polyps.
3.Circulating immunological transcriptomic profile identifies DDX3Y and USP9Y on the Y chromosome as promising biomarkers for predicting response to programmed death 1/programmed death ligand 1 blockade.
Liting YOU ; Zhaodan XIN ; Feifei NA ; Min CHEN ; Yang WEN ; Jin LI ; Jiajia SONG ; Ling BAI ; Jianzhao ZHAI ; Xiaohan ZHOU ; Binwu YING ; Juan ZHOU
Chinese Medical Journal 2025;138(3):364-366
4.Exploration of pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in treatment of gouty arthritis based on UPLC-Q-Exactive Orbitrap-MS technology and network pharmacology.
Yan XIAO ; Ting ZHANG ; Ying-Jie ZHANG ; Bin HUANG ; Peng CHEN ; Xiao-Hua CHEN ; Ming-Qing HUANG ; Xue-Ting CHEN ; You-Xin SU ; Jie-Mei GUO
China Journal of Chinese Materia Medica 2025;50(2):444-488
Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use*
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Network Pharmacology
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Arthritis, Gouty/metabolism*
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Chromatography, High Pressure Liquid/methods*
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Humans
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Mass Spectrometry/methods*
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Protein Interaction Maps/drug effects*
5.Processing technology of calcined Magnetitum based on concept of QbD and its XRD characteristic spectra.
De-Wen ZENG ; Jing-Wei ZHOU ; Tian-Xing HE ; Yu-Mei CHEN ; Huan-Huan XU ; Jian FENG ; Yue YANG ; Xin CHEN ; Jia-Liang ZOU ; Lin CHEN ; Hong-Ping CHEN ; Shi-Lin CHEN ; Yuan HU ; You-Ping LIU
China Journal of Chinese Materia Medica 2025;50(9):2391-2403
Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods*
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Drugs, Chinese Herbal/chemistry*
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Quality Control
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Particle Size
6.Chinese Medicine for Treatment of COVID-19: A Review of Potential Pharmacological Components and Mechanisms.
Qian-Qian XU ; Dong-Dong YU ; Xiao-Dan FAN ; He-Rong CUI ; Qian-Qian DAI ; Xiao-Ying ZHONG ; Xin-Yi ZHANG ; Chen ZHAO ; Liang-Zhen YOU ; Hong-Cai SHANG
Chinese journal of integrative medicine 2025;31(1):83-95
Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans
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Drugs, Chinese Herbal/pharmacology*
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COVID-19 Drug Treatment
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SARS-CoV-2/drug effects*
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COVID-19/therapy*
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Medicine, Chinese Traditional/methods*
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Antiviral Agents/pharmacology*
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Animals
7.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
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Pulmonary Disease, Chronic Obstructive/epidemiology*
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Exercise
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Male
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Female
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Middle Aged
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Prospective Studies
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Aged
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Genetic Predisposition to Disease
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Risk Factors
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United Kingdom/epidemiology*
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Incidence
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Adult
8.Analysis of temporal trends of the incidence rate of tuberculosis in Shaanxi Province
Hengliang LYU ; Hongwei ZHANG ; Hui CHEN ; Xihao LIU ; Xueli ZHANG ; Xin ZHANG ; Junzhu BAI ; Shumeng YOU ; Yuanyong XU ; Wenyi ZHANG
Chinese Journal of Preventive Medicine 2024;58(11):1659-1664
Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.
9.Construction and application of big data sharing platform for clinical scientific research
You-Qiong CHEN ; Qing-Ke SHI ; Mi-Ye WANG ; Ren-Xin DING ; Xue-Jun ZHUO
Chinese Medical Equipment Journal 2024;45(4):27-31
Objective To construct a big data sharing platform for clinical scientific research to solve the problems of clinical research in decentralized application systems and data sharing safety.Methods A clinical research information data usage management system was developed through the formulation of management methods in line with the actual situation of the institution,normalized standard data usage processes and a data usage service team.Then a clinical scientific research big data sharing platform including the components for sharing environment construction,research application integration,data desensitization and encryption and file management was established based on the existing hospital systems,the requirements of clinical research data usage management and the habits of clinical researchers.Results The platform realized the balance between open sharing of clinical research data and data security control,which improved the efficiency of clinical researchers while reducing data security risks during data transmission and data analysis.Conclusion The clinical scientific research big data sharing platform meets the needs of clinical scientific research application and data security management,and provides references for the co-construction-sharing of medical big data resources.[Chinese Medical Equipment Journal,2024,45(4):27-31]
10.Study on cerebral perfusion and cerebral functional connectivity in patients with neuromyelitis optica spectrum disorder
Juan CHEN ; Ting YOU ; Chuan YUAN ; Tingting YUAN ; Xin SHI ; Hui DAI
Journal of Practical Radiology 2024;40(8):1224-1227
Objective To investigate the changes in cerebral blood flow(CBF)and whole-brain functional connectivity(FC)in patients with neuromyelitis optica spectrum disorder(NMOSD)examined by conventional MRI.Methods Twenty-two patients with NMOSD and 25 matched healthy controls(HC)were included,and all subjects'conventional MRI sequences,arterial spin labeling(ASL),and resting-state functional magnetic resonance imaging(rs-fMRI)image data were acquired,and the brain regions with CBF differences between groups extracted based on ASL were used as seed points for whole-brain FC analysis,the FC differences between the groups were compared,and the correlation between the parameter values and the expanded disability status scale(EDSS)scores were analyzed.Results NMOSD patients exhibited a decrease in CBF value in the right supratemporal gyrus,bilateral calcarine fissure and right supplementary motor area,while the right middle temporal gyrus displayed an increase when compared to HC.Whole-brain FC analysis based on seed points revealed an increase in FC value between bilateral calcarine fissure and olfactory cortex,as well as between right supplementary motor area and left superior frontal gyrus.While FC value between the right supplementary motor area and left precentral gyrus,bilateral thalamus,right supraoccipital gyrus were decreased.The FC value between the right supratemporal gyrus and right inferior parietal lobule,left supratemporal gyrus,right precuneus lobes showed a decrease[Gaussian random field(GRF)-corrected,P<0.05].There was a correlation between CBF values of bilateral calcarine fissure and EDSS scores in NMOSD patients(rs=-0.456,P=0.033).Conclusion There are CBF and FC abnormalities in multiple brain regions in NMOSD patients,which provide imaging basis and insights for the brain micropathological changes of NMOSD,and help to understand the pathology and neural mechanism of NMOSD.


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