1.Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition)and their series interpretation(7):selection of control groups
Qinxi TIAN ; Siyan ZHAN ; Feng SUN ; Zhirong YANG
Chinese Journal of Pharmacoepidemiology 2025;34(7):725-733
The selection of an appropriate control group is a critical component of pharmacoepidemiologic research.This article provides an interpretation of the control selection methods outlined in the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition).According to the 2nd edition,studies are categorized into interventional and non-interventional research.In interventional research,control group options include placebo controls,no-treatment controls,active controls,and dose-response controls.For non-interventional research,the gold standard design is the active comparator new user(ACNU)design.When the ACNU design is not feasible,alternative control group strategies should be selected based on the research objective,data sources,exposure characteristics,and potential confounding.These alternatives may include non-user comparators,prevalent user comparators,self-controlled comparators,and external controls.Finally,this article compares the applicability,strengths,and limitations of various control group types.It aims to provide methodological guidance for the scientific selection of control groups in pharmacoepidemiologic studies and to support the conduct of high-quality research.
2.Reassessing the scope of real-world data applications and the value of real-world evidence
Feng SUN ; Meng ZHANG ; Houyu ZHAO ; Zhirong YANG ; Junli ZHU ; Jing LI ; Linong JI ; Jiefu YANG ; Siyan ZHAN
Chinese Journal of Epidemiology 2025;46(6):1079-1084
In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.
3.Value of using ultrasound features to improve the Ovarian-Adnexal Image Reporting and Data System Category 4 in the benign-malignant differential diagnosis of ovarian-adnexal masses
Lei WU ; Yingnan WU ; Jing ZHAO ; Liping GONG ; Shuang ZHANG ; Jiawei TIAN ; Zhirong HE ; Litao SUN
Chinese Journal of Ultrasonography 2025;34(3):232-238
Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System(O-RADS)Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers[the Second Afliated Hospital of Harbin Medical University(188 cases),Zhejiang Provincial People's Hospital(146 cases),Sichuan Provincial Maternity and Child Health Care Hospital(90 cases),and Fuling Hospital of Chongqing University(77 cases)]from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers(the Second Hospital of Harbin Medical University,Zhejiang Provincial People's Hospital,and Sichuan Maternal and Child Health Hospital)were randomly divided into a training group(339 cases)and an internal validation group(85 cases)according to an 8∶2 randomization,while the cases from the other clinical center(Fuling Hospital of Chongqing University)were selected as the external validation group(77 cases),and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis,and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve(AUC)was calculated,and it was validated in the internal validation group and the external validation group;and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components,≥ 4 papillary projections,smooth inner wall of the cyst,color flow score ≥ 3 points,and acoustic shadowing were independent predictors of ovarian cancer(all P < 0.05);while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer(all P < 0.05),and smooth cyst walls and acoustic shadows were independent protective factors(all P < 0.05).The diagnostic accuracies of the modified training group,internal validation group,and external validation group were 73.7%,68.2%,70.1%,respectively,which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS(38.9%,37.6%,33.8%)(all P < 0.05).The diagnostic sensitivity,specificity and AUC of the training group were 0.871,0.652,0.762,respectively,while the internal validation group were 0.844,0.585,0.714,and 0.846,0.627,0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.
4.Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.
Sijia ZHAO ; Yanyan YANG ; Hong LI ; Pin SUN ; Xiangqin HE ; Chao WANG ; Jingjing ZHANG ; Yu TIAN ; Tao YU ; Zhirong JIANG
Acta Pharmaceutica Sinica B 2025;15(10):5127-5144
Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.
5.Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate aging in mice.
Sipeng WU ; Yiqi CAI ; Lixiao ZHANG ; Xiang LI ; Xu LIU ; Guangkeng ZHOU ; Hongdi LUO ; Renjian LI ; Yujia HUO ; Zhirong ZHANG ; Siyi CHEN ; Jinliang HUANG ; Jiahao SHI ; Shanwei DING ; Zhe SUN ; Zizhuo ZHOU ; Pengcheng WANG ; Geng WANG
Protein & Cell 2025;16(1):28-48
One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals
;
Mice
;
RNA, Untranslated/metabolism*
;
Aging/genetics*
;
Mice, Transgenic
;
Telomerase/metabolism*
;
RNA/genetics*
;
Hippocampus/metabolism*
;
Humans
;
Mice, Inbred C57BL
6.Clinical research progress of efgartigimod in the treatment of general-ized myasthenia gravis
Shu LIU ; Chunhui SUN ; Zhirong TAN ; Man XING
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(5):714-720
Myasthenia gravis(MG)is a chronic autoimmune disease that causes partial or system-ic skeletal muscle weakness and fatigue.Efgartigi-mod is an antibody fragment targeting the Fc re-ceptor in newborns,which clears pathogenic immu-noglobulin G antibodies through a unique mecha-nism.Efgartigimod is used to treat systemic myas-thenia gravis safely and efficiently,which can signif-icantly improve muscle strength and quality of life for patients.This article reviews pharmacological,clinical research,and safety of efgartigimod,in or-der to providing reference for its clinical treatment in systemic myasthenia gravis(gGM).
7.Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition)and their series interpretation(7):selection of control groups
Qinxi TIAN ; Siyan ZHAN ; Feng SUN ; Zhirong YANG
Chinese Journal of Pharmacoepidemiology 2025;34(7):725-733
The selection of an appropriate control group is a critical component of pharmacoepidemiologic research.This article provides an interpretation of the control selection methods outlined in the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition).According to the 2nd edition,studies are categorized into interventional and non-interventional research.In interventional research,control group options include placebo controls,no-treatment controls,active controls,and dose-response controls.For non-interventional research,the gold standard design is the active comparator new user(ACNU)design.When the ACNU design is not feasible,alternative control group strategies should be selected based on the research objective,data sources,exposure characteristics,and potential confounding.These alternatives may include non-user comparators,prevalent user comparators,self-controlled comparators,and external controls.Finally,this article compares the applicability,strengths,and limitations of various control group types.It aims to provide methodological guidance for the scientific selection of control groups in pharmacoepidemiologic studies and to support the conduct of high-quality research.
8.Reassessing the scope of real-world data applications and the value of real-world evidence
Feng SUN ; Meng ZHANG ; Houyu ZHAO ; Zhirong YANG ; Junli ZHU ; Jing LI ; Linong JI ; Jiefu YANG ; Siyan ZHAN
Chinese Journal of Epidemiology 2025;46(6):1079-1084
In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.
9.Clinical research progress of efgartigimod in the treatment of general-ized myasthenia gravis
Shu LIU ; Chunhui SUN ; Zhirong TAN ; Man XING
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(5):714-720
Myasthenia gravis(MG)is a chronic autoimmune disease that causes partial or system-ic skeletal muscle weakness and fatigue.Efgartigi-mod is an antibody fragment targeting the Fc re-ceptor in newborns,which clears pathogenic immu-noglobulin G antibodies through a unique mecha-nism.Efgartigimod is used to treat systemic myas-thenia gravis safely and efficiently,which can signif-icantly improve muscle strength and quality of life for patients.This article reviews pharmacological,clinical research,and safety of efgartigimod,in or-der to providing reference for its clinical treatment in systemic myasthenia gravis(gGM).
10.Value of using ultrasound features to improve the Ovarian-Adnexal Image Reporting and Data System Category 4 in the benign-malignant differential diagnosis of ovarian-adnexal masses
Lei WU ; Yingnan WU ; Jing ZHAO ; Liping GONG ; Shuang ZHANG ; Jiawei TIAN ; Zhirong HE ; Litao SUN
Chinese Journal of Ultrasonography 2025;34(3):232-238
Objective:To explore the value of ultrasound features modified version 2022 of the Ovarian-Adnexal Imaging Reporting and Data System(O-RADS)Category 4 in the differential diagnosis of benign and malignant ovarian-adnexal tumors.Methods:Retrospective analysis was conducted in 501 cases with ovarian masses classified into 4 categories according to the 2022 version of O-RADS who were collected from 4 clinical centers[the Second Afliated Hospital of Harbin Medical University(188 cases),Zhejiang Provincial People's Hospital(146 cases),Sichuan Provincial Maternity and Child Health Care Hospital(90 cases),and Fuling Hospital of Chongqing University(77 cases)]from January 2018 to July 2024 with concomitant surgical resection.The 424 cases from 3 of the clinical centers(the Second Hospital of Harbin Medical University,Zhejiang Provincial People's Hospital,and Sichuan Maternal and Child Health Hospital)were randomly divided into a training group(339 cases)and an internal validation group(85 cases)according to an 8∶2 randomization,while the cases from the other clinical center(Fuling Hospital of Chongqing University)were selected as the external validation group(77 cases),and the pathological diagnosis was used as the “gold standard”.Univariate and multifactorial logistic regression analyses were performed on the ultrasound characteristics of the training group to screen the independent predictors associated with ovarian carcinogenesis,and to formulate the stratification rules for the 4 types of masses in O-RADS. The ROC curve of this stratification method was plotted and the area under the curve(AUC)was calculated,and it was validated in the internal validation group and the external validation group;and the diagnostic accuracy was compared with that of the 2022 version of O-RADS.Results:Univariate logistic analysis showed that cysts with solid components,≥ 4 papillary projections,smooth inner wall of the cyst,color flow score ≥ 3 points,and acoustic shadowing were independent predictors of ovarian cancer(all P < 0.05);while multifactorial logistic analysis showed that cysts with a solid component and a color flow score ≥3 points were independent risk factors of ovarian cancer(all P < 0.05),and smooth cyst walls and acoustic shadows were independent protective factors(all P < 0.05).The diagnostic accuracies of the modified training group,internal validation group,and external validation group were 73.7%,68.2%,70.1%,respectively,which were significantly higher than the diagnostic accuracies of the 2022 version of the O-RADS(38.9%,37.6%,33.8%)(all P < 0.05).The diagnostic sensitivity,specificity and AUC of the training group were 0.871,0.652,0.762,respectively,while the internal validation group were 0.844,0.585,0.714,and 0.846,0.627,0.737 in the external validation group. Conclusions:Improvement of the 2022 version of O-RADS category 4 using ultrasound features may improve the identification of benign and malignant ovarian-adnexal tumors.

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