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.The impact of DRGs payment on Traditional Chinese Medicine hospitals:Based on difference-in-difference analysis
Hui-Jun GUO ; Jing LIU ; Guang-Yu HU ; Yi-Wei HAO ; Xin-Mei HAO ; Ya-Nan WANG ; Hui-Dong ZHU ; Qiu-Yan LI
Chinese Journal of Health Policy 2024;17(6):47-55
Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.
3.The Role of Spinal Cord Compression in Predicting Intraoperative Neurophysiological Monitoring Events in Patients With Kyphotic Deformity: A Magnetic Resonance Imaging-Based Study
Zhen JIN ; Jie LI ; Hui XU ; Zongshan HU ; Yanjie XU ; Ziyang TANG ; Yong QIU ; Zhen LIU ; Zezhang ZHU
Neurospine 2024;21(2):701-711
Objective:
To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity.
Methods:
Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types.
Results:
A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215–48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126– 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966–9.727; p < 0.001) was confirmed as an independent risk factor for IONM events.
Conclusion
We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.
4.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
5.Stress analysis of trabecular hip prosthesis stem implantation
Bo LI ; Li-Lan GAO ; Ya CHEN ; Shu-Hong LIU ; Ya-Hui HU ; Lin-Wei LYU ; Jin-Duo YE ; Chun-Qiu ZHANG
Chinese Medical Equipment Journal 2024;45(3):29-35
Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5%and 14.7%compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]
6.The Role of Spinal Cord Compression in Predicting Intraoperative Neurophysiological Monitoring Events in Patients With Kyphotic Deformity: A Magnetic Resonance Imaging-Based Study
Zhen JIN ; Jie LI ; Hui XU ; Zongshan HU ; Yanjie XU ; Ziyang TANG ; Yong QIU ; Zhen LIU ; Zezhang ZHU
Neurospine 2024;21(2):701-711
Objective:
To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity.
Methods:
Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types.
Results:
A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215–48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126– 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966–9.727; p < 0.001) was confirmed as an independent risk factor for IONM events.
Conclusion
We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.
7.The Role of Spinal Cord Compression in Predicting Intraoperative Neurophysiological Monitoring Events in Patients With Kyphotic Deformity: A Magnetic Resonance Imaging-Based Study
Zhen JIN ; Jie LI ; Hui XU ; Zongshan HU ; Yanjie XU ; Ziyang TANG ; Yong QIU ; Zhen LIU ; Zezhang ZHU
Neurospine 2024;21(2):701-711
Objective:
To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity.
Methods:
Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types.
Results:
A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215–48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126– 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966–9.727; p < 0.001) was confirmed as an independent risk factor for IONM events.
Conclusion
We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.
8.Formulation and Analysis on the Standard of Pharmacy Practice in e-Hospital
Qian ZHANG ; Xiaoyan QIU ; Hui ZHAO ; Dan MEI ; Xiaoyang LU ; Pinfang HUANG ; Dong LIU ; Mingkang ZHONG ; Jiancun ZHEN
Herald of Medicine 2024;43(7):1061-1065
Pharmacy practice in e-hospital is an innovative form that greatly enhances the accessibility,efficiency,and convenience of medical services,providing continuous health management and chronic disease drug treatment management for patients.To ensure the quality of pharmacy practice in e-hospitals,the standard formulation team for pharmacy practice in e-hospitals adhered to the principles of scientific,universal,instructive,and operability.They comb through key management content from national policy documents,domestic and international standards and regulations,and literature analysis.Combined with the actual work situation of pharmacy practice in e-hospitals,the standard is formulated through multiple rounds of opinion collection and expert verification.This paper interprets the key content of the standard,including basic requirements,service content and processes,and quality management and evaluation improvement,to provide guidance and reference for managers and pharmacists to deeply understand the standard and further enhance the quality of pharmacy practice in e-hospitals.
9.A multicenter retrospective cohort study on the attributable risk of patients with Acinetobacter baumannii sterile body fluid infection
Lei HE ; Dao-Bin JIANG ; Ding LIU ; Xiao-Fang ZHENG ; He-Yu QIU ; Shu-Mei WU ; Xiao-Ying WU ; Jin-Lan CUI ; Shou-Jia XIE ; Qin XIA ; Li HE ; Xi-Zhao LIU ; Chang-Hui SHU ; Rong-Qin LI ; Hong-Ying TAO ; Ze-Fen CHEN
Chinese Journal of Infection Control 2024;23(1):42-48
Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
10.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Result Analysis
Print
Save
E-mail