1.The Solomon Four-Group Design:Key Considerations in Design and Statistical Analysis and Their Significance in Clinical Trials of Traditional Chinese Medicine
Wenqian ZHANG ; Yufei LI ; Tong LIN ; Xintong WEI ; Yingjie WANG ; Jianping LIU ; Ying ZHANG
Journal of Traditional Chinese Medicine 2025;66(16):1649-1655
The Solomon four-group design, a critical method for improving internal validity in clinical research, can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results, which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design, summarized its applications in clinical research at home and abroad, explored its advantages and limitations, and discussed the potential value in traditional Chinese medicine (TCM) clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies, and reduce the bias in the evaluation of subjective indicators. Meanwhile, given the complexity of the Solomon four-group design and the particularity of TCM clinical research, it is proposed that future TCM clinical studies should focus on using psychological scales, know-ledge, attitude, and behavior measurements, and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.
2.Tumor-intrinsic PRMT5 upregulates FGL1 via methylating TCF12 to inhibit CD8+ T-cell-mediated antitumor immunity in liver cancer.
Jiao SUN ; Hongfeng YUAN ; Linlin SUN ; Lina ZHAO ; Yufei WANG ; Chunyu HOU ; Huihui ZHANG ; Pan LV ; Guang YANG ; Ningning ZHANG ; Wei LU ; Xiaodong ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):188-204
Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8+ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8+ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.
3.Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis.
Yufei HUI ; Xue JIAO ; Li YANG ; Dejin LU ; Yanbo HAN ; Wen YANG ; Yanli CAO ; Yuxi MIAO ; Shiqiang GONG ; Minjie WEI
Acta Pharmaceutica Sinica B 2025;15(7):3404-3418
Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.
4.Identification of potential immune-related mechanisms related to the development of multiple myeloma
Yaomei WANG ; Wenli ZHANG ; Tiandong LI ; Mengmeng LIU ; Mengya GAO ; Xinqing LI ; Yufei CHEN ; Yongping SONG ; Wei LI ; Chunyan DU ; Fang WANG ; Lina LIU
Chinese Medical Journal 2024;137(13):1603-1613
Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.
5.A study of the performance evaluation of iCBCT imaging mode
Qingxin WANG ; Qifeng LI ; Wei WANG ; Zhongqiu WANG ; Yufei WANG ; Chengbin QU ; Chunyin LI ; Wenwen ZHANG ; Zhiyong YUAN ; Yu SA
Chinese Journal of Radiation Oncology 2024;33(3):237-243
Objective:To comprehensively evaluate the performance of the iterative cone beam CT (iCBCT) imaging mode of Varian linear accelerators and to explore its specific advantages in clinical application.Methods:The kV cone beam CT (CBCT) imaging systems of Halcyon 2.0, Edge, and VitalBeam linear accelerators from Tianjin Medical University Cancer Institute & Hospital were selected, among which Halcyon 2.0 and Edge were equipped with the iCBCT imaging mode. The Penta-Guide phantom was used to evaluate the registration accuracy of iCBCT imaging modes. The accuracy of treatment couch position was measured by a ruler. The image quality of the iCBCT and conventional CBCT modes of various imaging devices were analyzed using the CatPhan604 phantom. The imaging beam-on time and reconstruction time were measured to assess image acquisition efficiency. The uniformity, spatial resolution, contrast, contrast-to-noise ratio (CNR), image acquisition time and reconstruction time between two imaging modes were statistically analyzed by t-test. Results:The maximum deviations of image registration measurement results of the iCBCT mode for Halcyon 2.0 and Edge accelerators compared to the standard values were 0.7 mm and 0.6 mm, respectively. The treatment couch position error of all devices was less than 1 mm. The iCBCT images under head scanning protocol primarily improved the uniformity and CNR. Compared to conventional CBCT images, Halcyon iCBCT increased the uniformity and CNR by 2.50% ( P<0.001) and 78.85% ( P<0.001), respectively, while Edge increased them by 2.18% ( P<0.001) and 86.42% ( P<0.001), both superior to VitalBeam CBCT images. Under pelvis scanning protocols, iCBCT images primarily improved the CNR compared to conventional CBCT images. Halcyon and Edge iCBCT increased the CNR by 113.57% ( P<0.001) and 133.87% ( P<0.001), respectively, both superior to VitalBeam CBCT images. In terms of image acquisition efficiency, the average reconstruction times for Halcyon and Edge iCBCT images increased by 7.28 s and 15.53 s, respectively, and the total image acquisition time of Halcyon accelerator was the shortest. Conclusions:While ensuring the registration accuracy, iCBCT imaging mode can significantly improve the CNR of images and improve the uniformity of images under head scanning protocol. The Halcyon imaging system can enhance image acquisition efficiency.
6.Construction and verification of a prediction nomogram for in-hospital death in elderly CHF patients based on noninvasive hemodynamic parameters
Mingyan YANG ; Wei CHEN ; Yang GAO ; Yanan HU ; Yuan LIU ; Yufei MA ; Yan YU ; Riuhan LIU ; Jiang YU ; Jian CAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):124-127
Objective To construct a nomogram model for predicting the risk of in-hospital death in CHF patients by using noninvasive hemodynamic monitoring combined with age,DBP,CRP and renal insufficiency(serum creatinine≥ 442 μmol/L).Methods A total of 223 elderly patients with acute onset of CHF admitted in First,Second Medical Centre of Chinese PLA General Hos-pital from September 2022 to March 2023 were recruited in this study.According to their clinical outcomes,they were divided into survival group(196 cases)and death group(27 cases).Based on the in-hospital death and other related indicators,a nomogram model was constructed to predict the risk factors of in-hospital death in CHF.Results Noninvasive hemodynamic mornitoring indi-cated that the death group had significantly higher LVEF and LCWI values but lower LVEDV value than the survival group(P<0.05,P<0.01).Multivariate logistic regression analysis showed that age(OR=1.131,95%CI:1.052-1.213,P=0.001),DBP(OR=0.932,95%CI:0.882-0.982,P=0.011),CRP(OR=1.171,95%CI:1.021-1.352,P=0.024),LVEDV(OR=0.984,95%CI:0.962-0.992,P=0.011)and renal insufficiency(OR=5.863,95%CI:1.351-1.731,P=0.004)were independent risk factors for the short-term prognosis of the elderly CHF patients.The AUC value of the nomogram model was 0.902(95%CI:0.819-0.948,P<0.05),and calibration curve analysis showed the C-index was 0.902,indicating accurate predictive perform-ance.Conclusion Age,DBP,LVEDV,CRP and renal insufficiency are independent risk factors for the short-term prognosis of the elderly CHF patients.
7.Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China
Zheng ZHANG ; Bing WU ; Yingli QU ; Yang LI ; Lanjing XU ; Chunxian LYU ; Chen CHEN ; Jun WANG ; Kai XUE ; Yuan WEI ; Jinhui ZHOU ; Xulin ZHENG ; Yidan QIU ; Yufei LUO ; Junxin LIU ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(2):227-234
Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.
8.Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China
Yufei LUO ; Yuan WEI ; Xiaochen WANG ; Yi ZHANG ; Wenli ZHANG ; Bing WU ; Zhengxiong YANG ; Xiaojie DONG ; Ruiting HAO ; Yifu LU ; Xiaoshuang FU ; Ziyue ZHU ; Ying ZHU ; Yuebin LYU ; Dongqun XU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2024;58(6):839-846
Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.
9.Expert Consensus on Standard Terminology for Hair Transplantation (2024 Edition)
Yong MIAO ; Wei WU ; Zhenyu GONG ; Wenjie JIANG ; Yufei LI ; Zhiqi HU ; Hua XIAN ; Xiang XIE ; Weiqi YANG ; Dongyi ZHANG ; Jufang ZHANG ; Jiaxian ZHANG ; Chunhua ZHANG ; HAIR TRANSPLANTATION EXPERT GROUP OF PLASTIC AND AESTHETIC NATIONAL MEDICAL QUALITY CONTROL CENTER
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1301-1310
In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the
10.Expert Consensus on Standard Terminology for Hair Transplantation (2024 Edition)
Yong MIAO ; Wei WU ; Zhenyu GONG ; Wenjie JIANG ; Yufei LI ; Zhiqi HU ; Hua XIAN ; Xiang XIE ; Weiqi YANG ; Dongyi ZHANG ; Jufang ZHANG ; Jiaxian ZHANG ; Chunhua ZHANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1301-1310
In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the

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