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.Excavation and evaluation of tocilizumab and infliximab for adverse drug event signals among children
Yue TAN ; Ning-Ning GE ; Jing PENG ; Wen-Shuang QIU ; Xin ZHANG ; Lan-Fang LI
The Chinese Journal of Clinical Pharmacology 2024;40(5):732-736
Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.
3.Discussion on hot topics and promotion paths for post-market surveillance and supervise of medical consumables based on non-active medical devices
Fang DONG ; Jianlong YANG ; Jiayue LI ; Peng NING ; Fangfang CHEN ; Shengnan SHI ; Xiaolan QIU ; Zigui XIE ; Zeshi CUI
China Medical Equipment 2024;21(2):166-173
Objective:To explore the research hotspots and effective promotion paths of post market surveillance and supervise of medical consumables with non-active medical devices.Methods:Data mining methods were used to collect related journal literatures and documents from the websites of China regulatory institutions and the China National Knowledge Infrastructure(CNKI),order sub item data of medical device adverse event reports,extract the MeSH element words of literatures and documents,perform bibliometric analysis and visual display.Results:The number of medical devices adverse event reports in China has been increasing year by year,reaching 694 866 in 2022,in the four statistical years from 2019 to 2022,the number of reports on non-active medical devices and IVD reagents also showed a parallel increasing trend,accounting for about 65.00% of the total number of adverse event reports on medical devices in the year.The bibliometric analysis of journal literature shows that research in this field has received varying degrees of participation from regulatory institutions,universities,medical institutions,and enterprises.Regulatory institutions have contributed 46 articles,accounting for 56.79% of the total number of articles,followed by 28 articles from universities.The co-occurrence analysis shows that hot topic is focused in 5 clusters:quality management,risk management,international experiences discussion and adverse event surveillance and re-evaluation and real-world research.China regulatory institutions attach great importance to post market surveillance and supervise,and have issued more than 20 relevant documents since 2006,focusing on specific topics and gradually deepening around safety and effectiveness.Conclusion:The post market surveillance and supervise of medical devices,especially medical consumables based on non-active medical devices,need to be promoted synchronously in three dimensions:regulatory institutions,medical institutions,and enterprises.Universities,research institutes,and industry organizations should work in coordinating to strengthen the collection,identification,and active surveillance of risk signals based on adverse event surveillance,safety evaluation based on risk management,and conducting real-world research,research and develop risk control and corrective and preventive measures.
4.Observation on the Safety of Chinese Medicine Combined with Immune Checkpoint Inhibitors for the Treatment of Non-small Cell Lung Cancer at Stage Ⅲ-Ⅳ
Lin ZHOU ; Si-Chong QIU ; Liu-Ning LI ; Xiao-Shu CHAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(5):1152-1159
Objective To investigate the clinical safety of Chinese medicine combined with immune checkpoint inhibitors(ICIs)for the treatment of non-small cell lung cancer(NSCLC)at stage Ⅲ-Ⅳ,and to explore the influencing factors of immune-related adverse events(irAEs)in the treatment of stage Ⅲ-Ⅳ NSCLC with ICIs.Methods A retrospective analysis was carried out for the investigation of the distribution of traditional Chinese medicine(TCM)syndromes,related medication information and the occurrence of irAEs in the hospitalized patients diagnosed as stage Ⅲ-Ⅳ NSCLC and treated with Chinese medicine combined with ICIs in the Oncology Department of Guangdong Provincial Hospital of Chinese Medicine(University-town Branch)from September 1,2019 to August 31,2022.And the levels of adverse reactions and their possible influencing factors were analyzed.Results(1)The treatment for the 90 NSCLC patients involved 4 regimens,namely ICIs monotherapy,ICIs combined with chemotherapy,ICIs combined with anti-angiogenic drugs,and ICIs combined with chemotherapy and anti-angiogenic drugs.Among them,ICIs combined with chemotherapy and anti-angiogenic drugs were used most frequently for 52 cases(49.1%).A total of 8 kinds of ICIs drugs were used,of which Tislelizumab accounted for the highest proportion(43 cases,40.6%).(2)All of the patients were classified into 5 syndrome types,namely qi deficiency and phlegm-stasis syndrome,phlegm-stasis obstructing the collateral syndrome,qi and yin deficiency syndrome,qi and blood deficiency syndrome,and phlegm-heat accumulation syndrome.Among them,qi deficiency and phlegm-stasis syndrome was the most common type(80 cases,88.9%).(3)The overall incidence of irAEs was 38.9%(35/90),and irAEs being or above grade 3(G3)level in the patients only accounted for 5.6%(5/90).The initial irAEs usually occurred at the immunotherapy course 1-3(17 cases,48.6%).The incidence of irAEs being or above G3 level in the patients treated with ICIs monotherapy was higher than that in the patients treated with the combined therapy(33.3%vs 3.6%).(4)The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score of 0-1(OR=8.218,95%CI:1.607-42.023,P = 0.011)and adrenal metastasis(OR=4.497,95%CI:1.237-16.354,P=0.022)were the independent risk factors for irAEs in patients with stageⅢ-Ⅳ NSCLC treated by ICIs(P<0.05).Conclusion Chinese medicine has the potential to reduce the incidnence of adverse reactions of ICIs in the treatment of stage Ⅲ-Ⅳ NSCLC.PS score of 0-1 and adrenal metastasis may be the independent risk factors for irAEs in patients with stage Ⅲ-Ⅳ NSCLC treated by ICIs.
5.Effects of esketamine combined with erector spinae block on the quality of early postoperative recov-ery in patients undergoing thoracoscopic surgery
Xiaoli NING ; Wei LIU ; Juan LI ; Cheng QIU ; Fenglei XIE ; Shengming YAN
The Journal of Clinical Anesthesiology 2024;40(5):473-477
Objective To investigate the effect of esketamine combined with erector spinae plane block(ESPB)on the quality of early postoperative recovery in patients undergoing thoracoscopic pulmonary surgery.Methods Ninety patients who underwent thoracoscopic lung surgery(thoracoscopic radical resec-tion of lung cancer,thoracoscopic lobectomy or segmentectomy)from May 2022 to July 2023 were selected,47 males and 43 females,aged 18-64 years,BMI 18-25 kg/m2,ASA physical statusⅠorⅡ.According to random number table method,the patients were divided into two groups:the ESPB group(group C)and the esketamine combined with ESPB group(group D),45 patients in each group.Patients in the two groups completed ultrasound-guided ESPB,followed by sufentanil anesthesia induction and patient-controlled intra-venous analgesia(PCIA)in group C,while esketamineanesthesia induction,maintenance,and PCIA in group D.The intraoperative dosage of anesthetics,numerical rating scale(NRS)score during activity 1 hour,6,12,24,and 48 hours after operation,the number of PCIA compressions within 24 hours after op-eration,the number of rescue analgesia after operation,the recovery time of anesthesia,the incidence of postoperative nausea and vomiting within 2 days after operation and the adverse reactions related to esket-amine were recorded.The 40-item recovery quality scale(QoR-40)score was used to evaluate the quality of recovery of patients 1 day before operation and 2 days after operation.The hospital anxiety and depression scale(HADS)was used to assess patients anxiety and depression 1 day before surgery and at discharge.Results Compared with group C,the dosage of propofol and remifentanil intraoperatively,the incidence of postoperative nausea and vomiting were decreased(P<0.05),the QoR-40 score was increased 2 days after operation,HADS score at discharge was decreased in group D(P<0.05).Conclusion Esketamine combined with ESPB is safe and effective for patients undergoing thoracoscopic lung surgery.The periopera-tive analgesia is perfect,the adverse reactions are few,and the quality of early recovery is high,which pro-vides a new anesthesia choice for such surgery.
6.Management of CT radiation dose in radiology department via applying Six Sigma management method
Haijing QIU ; Jiayi DU ; Tianlai LI ; Zhigang JI ; Qi PAN ; Ning WANG ; Chunhai LUO
Journal of Practical Radiology 2024;40(7):1165-1169
Objective To enhance CT radiation dose management in radiology department via applying Six Sigma management method.Methods The radiation quality control processes in the radiology department were optimized according to the Six Sigma quality management DMAIC pattern.The volume CT dose index(CTDIvol),dose length product(DLP),radiation quality control problems of adult and pediatric CT scans from January 2022 to February 2022 were collected as baseline data,and data collected from August 2022 to September 2022 were taken as the control group for analysis via Six Sigma management method.All data of the dose values and problem rates were compared and analyzed between before and after Six Sigma management methods.Results The DLP in the adult group was decreased by 65.5%in computed tomography urography(CTU),decreased by 25.5%in neck enhancement,decreased by 9.8%in head,decreased by 24%in facial cranial,and decreased by 27.7%in chest enhancement,with a statistical difference(P<0.05).While DLP in the adult group was decreased by 9.7%in abdominal enhancement,with no significant difference(P>0.05).The DLP in the pediatric(<1 year)group was increased by 35%in head scans,with no significant difference(P>0.05).While the DLP was decreased by 30.2%in 1 to 5 years group,decreased by 21.8%in 6 to 10 years group,decreased by 27.6%in 11 to 15 years group,with statistical difference(P<0.05).The DLP of facial cranial was decreased by 43.3%in 6 to 10 years group,decreased by 29.1%in 11 to 15 years group,with statistical difference(P<0.05).The DLP of chest was decreased by 13%in<1 year group(P>0.05),increased by 2.2%in 1 to 5 years group(P>0.05),decreased by 42.6%in 6 to 10 years group,decreased by 54.2%in 11 to 15 years group(P<0.05).The incidence of radiological quality control problems of after Six Sigma management was significantly lower than that of before Six Sigma management(P<0.05).Conclusion Six Sigma management method can identify problems in the clinical practice and enhance the ability of radiation quality control through optimization.
7.Analysis of WHO Global Patient Safety Report 2024 and related medical device issues
Zhiyong LI ; Ying ZHANG ; Zeshi CUI ; Wei SONG ; Xiaorui ZHAO ; Peng NING ; Xiaolan QIU ; Zixin KANG
China Medical Equipment 2024;21(8):198-204
Based on the perspective of medical equipment safety culture,analyze the Global Patient Safety Report 2024 released by the World Health Organization(WHO)on May 30,and extract patient safety elements related to medical devices.Propose to initiate action plan for patient safety related to medical devices and discuss the pathway and measures to further ensure patient safety and strengthen safety management in the clinical use of medical devices,in conjunction with promoting high-quality development of hospitals.
8.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
9.Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi.
Ning-Ye FANG ; Wen-Cui WEI ; Jian-Jun LI ; Ping CEN ; Xian-Xiang FENG ; Dong YANG ; Kai-Ling TANG ; Shu-Jia LIANG ; Yu-Lan SHAO ; Hua-Xiang LU ; He JIANG ; Qin MENG ; Shuai-Feng LIU ; Qiu-Ying ZHU ; Huan-Huan CHEN ; Guang-Hua LAN ; Shi-Xiong YANG ; Li-Fang ZHOU ; Jing-Lin MO ; Xian-Min GE
Acta Academiae Medicinae Sinicae 2023;45(3):399-404
Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male
;
Humans
;
Middle Aged
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Reverse Transcriptase Inhibitors/therapeutic use*
;
HIV Infections/drug therapy*
;
Drug Resistance, Viral/genetics*
;
China/epidemiology*
;
Mutation
;
HIV-1/genetics*
;
Protease Inhibitors/therapeutic use*
;
Genotype
10.Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China.
Xiao Qi GUO ; Shuang ZHANG ; Hui ZHENG ; Feng WANG ; Ning MIAO ; Qiu Dong SU ; Sheng Li BI ; Guo Min ZHANG ; Fu Zhen WANG ; Li Ping SHEN
Chinese Journal of Epidemiology 2023;44(5):759-764
Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.
Humans
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Asian People
;
China/epidemiology*
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Ethnicity
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Genotype
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Gerbillinae
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Hepatitis B virus/genetics*
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Hepatitis B/virology*

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