1.Novel Structural Features of Isoflavone Synthase from Medicago truncatula Shed Light on Its Unique Enzymatic Mechanism
Chao SHI ; Zhao-Yang YE ; Fei XU ; Xiang-Ning DU ; Zhang-Xin CHEN ; Ming-Yue GU ; Jie DENG ; Wei WANG ; Liang-Yu LIU ; Mei-Ying WANG ; Xiao-Dong SU ; He-Li LIU ; Ming-Ying SHANG ; Li-Xin HUANG ; Zhen-Zhan CHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1204-1213,中插1-中插6
Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.
2.Progresses of structural and functional MRI in research of hippocampal changes in Alzheimer disease continuum
Qingqing SHANG ; Bingyuan CHU ; Ming YANG ; Hanxi ZHANG ; Xinlu LI ; Ze FENG ; Weiqing LI ; Feng WANG
Chinese Journal of Medical Imaging Technology 2025;41(9):1595-1599
Alzheimer disease(AD)is a neurological disease characterized by cognitive decline.AD continuum refers to the dynamic development progression from early pathological changes to obvious clinical symptoms,covering the continuous spectrum of subjective cognition decline(SCD)stage,mild cognitive impairment(MCI)stage and dementia stage.As one of the key brain regions involved in early stage,hippocampus(HP)in AD continuum is closely related to the progression of disease.MRI has been widely used in the study of HP in the AD continuum.The progresses in structural and functional MRI research of HP changes in AD continuum were reviewed in this article.
3.Standardization Study on the Pathogenesis of Cough in TCM and Preliminary Exploration on the Category Structure of"Pathogenesis-syndrome"
Sixing ZHU ; Shiyun YAN ; Li SHANG ; Lina YANG ; Ming LI ; Liyun CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(7):19-24
Objective To explore the principles and methods for extracting terminology related to the pathogenesis of cough disease,as well as the standardization issues in constructing the category structure of"pathogenesis-syndrome";To provide references for standardized research on the pathogenesis of cough disease.Methods The principle of defining the pathogenesis of cough disease was based on the physiological dysfunction and pathological characteristics of lung manifestation.Using ontology technology,literature induction,comparative analysis and other methods,with the help of terminology concepts,Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases and important ancient books of TCM throughout history related to the pathogenesis of cough disease were sorted,summarized,and extracted.The relationship between the"pathogenesis-syndrome"category of cough disease was analyzed and the structure was constructed.Results Preliminary principles and methods for standardizing the extraction of pathogenesis terminology of cough disease were formulated,including screening scope,inclusion and exclusion criteria,etc.The content of cough disease entries in Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases was defined for pathogenesis terminology,and the hierarchical structure of terminology was established to clarify the connotation and extension of terminology,thereby determining the category relationship of terminology and forming a category structure of"pathogenesis-syndrome"mapping relationship.On this basis,by extracting pathogenesis terms of cough disease from important ancient books of TCM throughout history,a category structure table of"pathogenesis-syndrome"for cough disease in TCM was formed.Conclusion On the basis of formulating standardized extraction principles and methods of pathogenesis terminology for TCM cough disease,a research model for the"pathogenesis-syndrome"category structure of TCM cough disease is constructed.This model has the characteristics of systematicity,clear hierarchical relationships,rich connotation of terminology,and extensibility,providing a new research paradigm for pathogenesis research.
4.Effect of different detector combinations on head CT image quality and radiation dose in 320-row CT
Yun LUO ; Ming-ran SHAO ; Shang-wen YANG ; Yu-xiao WANG ; Kang SHI ; Ya-yun XU
Chinese Medical Equipment Journal 2025;46(4):57-62
Objective To compare the effects of different detector combinations of 320-row CT on the image quality and radiation dose of head CT to explore the feasibility of using a wide detector for head CT scanning.Methods Totally 100 patients underwent head CT scanning due to trauma or cerebrovascular disease at some hospital from June to August 2023 were collected prospectively and divided into group A and group B by using block randomization grouping method,with the length of the block group being 2 and 50 patients in each group.In group A,all the detectors had the widths at z-axis direction being 40×0.5 mm and head scanning was completed after multiple exposures;in group B,detector combinations with widths of 280×0.5 mm or 320×0.5 mm were chosen based on the patient's head size in the head-foot direction(z-axis direction),and head scanning was performed with a single-turn exposure.The remaining scanning and image reconstruction parameters in the two groups were kept completely consistent.The head image quality of the 2 groups was evaluated objectively and scored subjectively by 2 radiologists.The volume CT dose index(CTDIvol),dose length product(DLP)and exposure time of the 2 groups were recorded,and the effective dose(ED)was calculated.SPSS 22.0 software was used for statistical analysis.Results In terms of objective evaluation of image quality,at the level of the parietal skull group B had the CT value of gray matter,image noise and contrast to noise ratio(CNR)of the images higher than those of group A,and the differences were statistically significant(all P<0.05);at the level of the posterior skull group B had the CT values of gray and white matter,image noise and air noise lower while CNR higher than those of group A,and the differences were statistically significant(all P<0.05).In terms of subjective scoring of image quality,at the levels of parietal and posterior skull group A behaved better than group B,and the differences were statistically significant(all P<0.05).In group A 5 patients had obvious motion artifacts affecting the diagnosis and the image quality scores not higher than 2,and secondary scanning had to be carried out;In group B all the patients had no obvious motion artifacts and met the diagnosis requirements.When compared with group A Group B had the CTDIvol,DLP,ED and exposure time decreased by 17.44%,17.24%,17.48%and 85.53%,respectively,and the differences were statistically significant(all P<0.05).Conclusion A wide detector gains advantages over a 20 mm detector in image quality when 320-row CT is used for head CT scanning,with the diagnosis requirements satisfied.[Chinese Medical Equipment Journal,2025,46(4):57-62]
5.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.
6.Progresses of structural and functional MRI in research of hippocampal changes in Alzheimer disease continuum
Qingqing SHANG ; Bingyuan CHU ; Ming YANG ; Hanxi ZHANG ; Xinlu LI ; Ze FENG ; Weiqing LI ; Feng WANG
Chinese Journal of Medical Imaging Technology 2025;41(9):1595-1599
Alzheimer disease(AD)is a neurological disease characterized by cognitive decline.AD continuum refers to the dynamic development progression from early pathological changes to obvious clinical symptoms,covering the continuous spectrum of subjective cognition decline(SCD)stage,mild cognitive impairment(MCI)stage and dementia stage.As one of the key brain regions involved in early stage,hippocampus(HP)in AD continuum is closely related to the progression of disease.MRI has been widely used in the study of HP in the AD continuum.The progresses in structural and functional MRI research of HP changes in AD continuum were reviewed in this article.
7.Effect of different detector combinations on head CT image quality and radiation dose in 320-row CT
Yun LUO ; Ming-ran SHAO ; Shang-wen YANG ; Yu-xiao WANG ; Kang SHI ; Ya-yun XU
Chinese Medical Equipment Journal 2025;46(4):57-62
Objective To compare the effects of different detector combinations of 320-row CT on the image quality and radiation dose of head CT to explore the feasibility of using a wide detector for head CT scanning.Methods Totally 100 patients underwent head CT scanning due to trauma or cerebrovascular disease at some hospital from June to August 2023 were collected prospectively and divided into group A and group B by using block randomization grouping method,with the length of the block group being 2 and 50 patients in each group.In group A,all the detectors had the widths at z-axis direction being 40×0.5 mm and head scanning was completed after multiple exposures;in group B,detector combinations with widths of 280×0.5 mm or 320×0.5 mm were chosen based on the patient's head size in the head-foot direction(z-axis direction),and head scanning was performed with a single-turn exposure.The remaining scanning and image reconstruction parameters in the two groups were kept completely consistent.The head image quality of the 2 groups was evaluated objectively and scored subjectively by 2 radiologists.The volume CT dose index(CTDIvol),dose length product(DLP)and exposure time of the 2 groups were recorded,and the effective dose(ED)was calculated.SPSS 22.0 software was used for statistical analysis.Results In terms of objective evaluation of image quality,at the level of the parietal skull group B had the CT value of gray matter,image noise and contrast to noise ratio(CNR)of the images higher than those of group A,and the differences were statistically significant(all P<0.05);at the level of the posterior skull group B had the CT values of gray and white matter,image noise and air noise lower while CNR higher than those of group A,and the differences were statistically significant(all P<0.05).In terms of subjective scoring of image quality,at the levels of parietal and posterior skull group A behaved better than group B,and the differences were statistically significant(all P<0.05).In group A 5 patients had obvious motion artifacts affecting the diagnosis and the image quality scores not higher than 2,and secondary scanning had to be carried out;In group B all the patients had no obvious motion artifacts and met the diagnosis requirements.When compared with group A Group B had the CTDIvol,DLP,ED and exposure time decreased by 17.44%,17.24%,17.48%and 85.53%,respectively,and the differences were statistically significant(all P<0.05).Conclusion A wide detector gains advantages over a 20 mm detector in image quality when 320-row CT is used for head CT scanning,with the diagnosis requirements satisfied.[Chinese Medical Equipment Journal,2025,46(4):57-62]
8.Standardization Study on the Pathogenesis of Cough in TCM and Preliminary Exploration on the Category Structure of"Pathogenesis-syndrome"
Sixing ZHU ; Shiyun YAN ; Li SHANG ; Lina YANG ; Ming LI ; Liyun CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(7):19-24
Objective To explore the principles and methods for extracting terminology related to the pathogenesis of cough disease,as well as the standardization issues in constructing the category structure of"pathogenesis-syndrome";To provide references for standardized research on the pathogenesis of cough disease.Methods The principle of defining the pathogenesis of cough disease was based on the physiological dysfunction and pathological characteristics of lung manifestation.Using ontology technology,literature induction,comparative analysis and other methods,with the help of terminology concepts,Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases and important ancient books of TCM throughout history related to the pathogenesis of cough disease were sorted,summarized,and extracted.The relationship between the"pathogenesis-syndrome"category of cough disease was analyzed and the structure was constructed.Results Preliminary principles and methods for standardizing the extraction of pathogenesis terminology of cough disease were formulated,including screening scope,inclusion and exclusion criteria,etc.The content of cough disease entries in Clinical Diagnosis and Treatment Terminology in Traditional Chinese Medicine Part 1:Diseases was defined for pathogenesis terminology,and the hierarchical structure of terminology was established to clarify the connotation and extension of terminology,thereby determining the category relationship of terminology and forming a category structure of"pathogenesis-syndrome"mapping relationship.On this basis,by extracting pathogenesis terms of cough disease from important ancient books of TCM throughout history,a category structure table of"pathogenesis-syndrome"for cough disease in TCM was formed.Conclusion On the basis of formulating standardized extraction principles and methods of pathogenesis terminology for TCM cough disease,a research model for the"pathogenesis-syndrome"category structure of TCM cough disease is constructed.This model has the characteristics of systematicity,clear hierarchical relationships,rich connotation of terminology,and extensibility,providing a new research paradigm for pathogenesis research.
9.Novel Structural Features of Isoflavone Synthase from Medicago truncatula Shed Light on Its Unique Enzymatic Mechanism
Chao SHI ; Zhao-Yang YE ; Fei XU ; Xiang-Ning DU ; Zhang-Xin CHEN ; Ming-Yue GU ; Jie DENG ; Wei WANG ; Liang-Yu LIU ; Mei-Ying WANG ; Xiao-Dong SU ; He-Li LIU ; Ming-Ying SHANG ; Li-Xin HUANG ; Zhen-Zhan CHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1204-1213,中插1-中插6
Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.
10.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

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