1.Huangqi Baijiang Yiren Decoction Restores Intestinal Mucosa Barrier in Rat Model of Ulcerative Colitis via miR-21/SOCS1/JAK1/STAT6 Signaling Pathway
Ruiping LI ; Shiyu WANG ; Xiunan WEI ; Ermei WU ; Dajuan SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):96-104
ObjectiveTo explore the potential mechanism by which Huangqi Baijiang Yiren decoction (HBY) repairs the intestinal mucosal injury in the rat model of ulcerative colitis (UC) via the miR-21/suppressor of cytokine signaling 1 (SOCS1)/Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6) signaling pathway. MethodsSixty SPF-grade male SD rats were randomly assigned into six groups: blank, model, low-dose (3.68 g·kg-1) HBY, medium-dose (7.35 g·kg-1) HBY, high-dose (14.5 g·kg-1) HBY, and mesalazine (0.035 g·kg-1), with 10 rats in each group. The rat model of UC was established in other groups except the blank group by 3% dextran sulfate sodium solution. The rats were administrated with corresponding drugs once a day for 7 consecutive days since the 3th day after modeling. The histopathological changes of the colon were observed by hematoxylin-eosin staining, and the Robarts histopathology index (RHI) was scored. Enzyme-linked immunosorbent assay was employed to measure the levels of pro-inflammatory cytokines [interleukin (IL)-6, IL-18, IL-1β, and tumor necrosis factor-α (TNF-α)] in the serum. Real-time PCR was employed to determine the mRNA levels of miR-21, SOCS1, JAK1, and STAT6 in the colon tissue. Western blot was employed to determine the protein levels of SOCS1, JAK1, phosphorylated (p)-JAK1, STAT6, p-STAT6, Occludin, and Claudin-1 in the colon tissue. ResultsCompared with the blank group, the model group showed an increase in disease activity index (DAI) (P<0.01), shortening of colon length (P<0.01), severe histopathological damage in the colon tissue, and an increase in RHI, rises in serum levels of IL-6, IL-1β, IL-18, and TNF-α (P<0.01), up-regulation in mRNA levels of miR-21, JAK1, and STAT6 and protein levels of p-JAK1 and p-STAT6 (P<0.01), and down-regulation in mRNA and protein levels of SOCS1 and protein levels of Occludin and Claudin-1 (P<0.01). The treatment with HBY reduced the DAI (P<0.01), alleviated colon shortening and histopathological damage in the colon tissue, decreased the RHI (P<0.01), lowered the serum levels of IL-6, IL-1β, IL-18, and TNF-α (P<0.01), down-regulated the mRNA levels of miR-21, JAK1, and STAT6 (P<0.05, P<0.01), up-regulated the mRNA level of SOCS1 (P<0.05), up-regulated the protein levels of SOCS1, Occludin, and Claudin-1 (P<0.05, P<0.01), and down-regulated the protein levels of p-JAK1 and p-STAT6 (P<0.05, P<0.01). ConclusionHBY may modulate the miR-21/SOCS1/JAK1/STAT6 signaling pathway to suppress inflammatory responses and restore the intestinal mucosal barrier in UC rats.
2.Introduction to Implementation Science Theories, Models, and Frameworks
Lixin SUN ; Enying GONG ; Yishu LIU ; Dan WU ; Chunyuan LI ; Shiyu LU ; Maoyi TIAN ; Qian LONG ; Dong XU ; Lijing YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1332-1343
Implementation Science is an interdisciplinary field dedicated to systematically studying how to effectively translate evidence-based research findings into practical application and implementation. In the health-related context, it focuses on enhancing the efficiency and quality of healthcare services, thereby facilitating the transition from scientific evidence to real-world practice. This article elaborates on Theories, Models, and Frameworks (TMF) within health-related Implementation Science, clarifying their basic concepts and classifications, and discussing their roles in guiding implementation processes. Furthermore, it reviews and prospects current research from three aspects: the constituent elements of TMF, their practical applications, and future directions. Five representative frameworks are emphasized, including the Consolidated Framework for Implementation Research (CFIR), the Practical Robust Implementation and Sustainability Model (PRISM), the Exploration, Preparation, Implementation, Sustainment (EPIS)framework, the Behavior Change Wheel (BCW), and the Normalization Process Theory (NPT). Additionally, resources such as the Dissemination & Implementation Models Webtool and the T-CaST tool are introduced to assist researchers in selecting appropriate TMFs based on project-specific needs.
3.Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.
Xudong LI ; Hong HUANG ; Fang WANG ; Mengjia LI ; Binglei ZHANG ; Jianxiang SHI ; Yuke LIU ; Mengya GAO ; Mingxia SUN ; Haixia CAO ; Danfeng ZHANG ; Na SHEN ; Weijie CAO ; Zhilei BIAN ; Haizhou XING ; Wei LI ; Linping XU ; Shiyu ZUO ; Yongping SONG
Chinese Medical Journal 2025;138(15):1866-1881
BACKGROUND:
Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets.
METHODS:
In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis.
RESULTS:
In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment.
CONCLUSIONS
This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans
;
Lymphoma, Large B-Cell, Diffuse/therapy*
;
Tumor Microenvironment/genetics*
;
Antigens, CD19/metabolism*
;
Leukemia, Myelomonocytic, Chronic/genetics*
;
Immunotherapy, Adoptive/adverse effects*
;
Male
;
Single-Cell Analysis/methods*
;
Female
;
Sequence Analysis, RNA/methods*
;
Receptors, Chimeric Antigen
;
Middle Aged
4.Sulfafurazole dimers potentiate chemo-immunotherapy of low immunogenic breast cancer by preventing the PD-L1 exosomes secretion.
Zheng WANG ; Ronghui YIN ; Lin ZHANG ; Shiyu LI ; Zhanwei ZHOU ; Minjie SUN
Acta Pharmaceutica Sinica B 2025;15(5):2673-2686
The αPD-L1 antibody-based immune checkpoint blockade therapy is still limited by the poor clinical response rate as it is mainly utilized to block surface PD-L1 on tumor cells while ignoring abundant PD-L1 exosomes secreted in the environment, causing tumor immune evasion. Here, we proposed an exosome biogenesis inhibition strategy to suppress tumor exosomes secretion from the source, reducing the inhibitory effect on T cells and enhancing chemo-immunotherapy efficacy. We developed sulfafurazole homodimers (SAS) with disulfide linkages, effectively releasing the drug in response to glutathione (GSH) and inhibiting 4T1 tumor-derived exosomes secretion. Subsequently, gemcitabine (Gem) was encapsulated to induce immunogenic cell death (ICD). Consequently, Gem@SAS inhibited the secretion of tumor exosomes by more than 70%, increased proliferation and granzyme B secretion ability of T cells by more than 2 times, and showed superior efficacy in breast cancer treatment as well as lung metastasis of breast cancer.
5.Research Progress in Anti-tumor Mechanisms of Prunellae Spica and Its Active Components
Mengqi LI ; Yu SHI ; Shiyu YANG ; Jieyu LI ; Yu HU ; Wenxiu SUN ; Lingjun LI
Chinese Journal of Modern Applied Pharmacy 2024;41(5):716-726
As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.
6.Advances on Chemical Constituents of Volatile Oil from Angelicae Sinensis Radix and Their Pharmacological Effect
Yu SHI ; Mengqi LI ; Shiyu YANG ; Yu HU ; Wenxiu SUN ; Lingjun LI
Chinese Journal of Modern Applied Pharmacy 2024;41(7):1006-1014
Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.
7.Overview of the ten global conferences on health promotion and implications for future work
Meichen SUN ; Shiyu LIU ; Wei WEI ; Zining WANG ; Xiangyang TIAN ; Liming LI ; Youfa WANG
Chinese Journal of Epidemiology 2024;45(4):591-596
Since 1986, the WHO has held ten global health promotion conferences covering various health promotion issues and sustainable development worldwide. These sessions have formed a series of consensus and actions that guide promoting health globally. This study analyzed the declarations, reports, and news materials from the ten conferences that studied health promotion action areas, focal topics, actor networks, partnership relationships, and other significant outcomes. It also explored how these conferences contributed to the construction and advancement of global health promotion consensus and actions. The first Global Conference on Health Promotion identified the concept of health promotion and five key action areas, laying the foundation for subsequent conferences and health promotion actions. Over the years, the ten conferences continuously expanded the essence of health promotion, developed partnership relationships, formulated public health promotion policies, and called for health promotion actions. This process culminated in the formation of global consensus and collective actions. The latter conferences have gained significant attention and influence. The conferences offer valuable insights for future global health promotion endeavors and provide global perspectives and pathways for the development of Healthy China.
8.The best evidence summary for blood glucose management in patients with end-stage diabetic kidney disease undergoing hemodialysis
Hongmei ZHANG ; Ning ZHANG ; Yujiao SUN ; Lili SHEN ; Yi LU ; Shiyu HAN
Chinese Journal of Practical Nursing 2024;40(1):43-50
Objective:To retrieve, evaluate and integrate the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, so as to provide a basis for clinical evidence-based nursing practice.Methods:BMJ Best Clinical Practice, Cochrane, OVID, Scopus, UpToDate, CNKI, Wanfang Database, Medical Pulse database, and other guideline networks and professional association websites and databases were searched for blood glucose management in hemodialysis patients with end-stage diabetic kidney disease. The search time limit was from the establishment of the database to May 10, 2023.Results:A total of 14 articles were included, including 1 clinical decision, 5 guidelines, 6 systematic reviews, 1 randomized controlled trial, and 1 expert consensus. The best evidences for blood glucose management in hemodialysis patients were summarized, including 8 aspects of pre-dialysis assessment, pre-dialysis blood glucose management, blood glucose management during dialysis, blood glucose management during dialysis interval, diet and nutrition, exercise management, lifestyle intervention and health education, with 25 pieces of evidence.Conclusions:This study summarizes the best evidence of blood glucose management in hemodialysis patients with end-stage diabetic kidney disease, and provides evidence-based basis for clinical practice for medical staff.
9.Optimization of DNA purification nano beads specifically for FFPE samples
Lin XIAO ; Xiaofang LÜ ; Shiyu CAO ; Dan JIANG ; Linyong SUN ; Kun LI ; Feng YE
Chinese Journal of Clinical and Experimental Pathology 2024;40(7):725-730
Purpose Focusing on the characteristics of for-malin fixed paraffin embedded(FFPE)samples,explored nano-magnetic bead nucleic acid extraction solutions with higher qual-ity/yield and continued to improve molecular pathology technolo-gy.Methods Alternative magnetic beads were synthesised in four major categories and 15 sub-categories and we screened to obtain high-quality/yield magnetic beads centred on FFPE samples.Simulated conventional tissues,simulated coarse needle punctures(liver),and simulated fiberoptic bronchoscopy sam-ples(lungs)were sectioned with the same number of serial slices in tubes.The nucleic acids of slices were extracted using the best magnetic beads screened in this study and common com-mercially available kits,and then perform comparison and purifi-cation quality parameters such as total amount and fragment size.The downstream applications of nucleic acids were validated by PCR and Sanger sequencing.Results Screening all homemade nanomagnetic beads centered on the DNA of FFPE samples,the total recoveries of the best performance nanomagnetic beads were obtained to be 58.5%±1.58%,and the total recoveries of five commercially available commercial magnetic beads and three do-mestic kit magnetic beads ranged from 18.68%to 40.71%.The total amount of DNA(ng)extracted from the same amount of tis-sue(serial slices),the nucleic acid yield of this study in simu-lated conventional tissues,simulated coarse needle punctures,and simulated fiberoptic bronchoscopy samples were increased by 39.49%-181.72%compared with those of the commercially a-vailable kits(P<0.05).The total amount of extracted nucleic acid from simulated fiberoptic bronchoscopy tissue sections can be more than 100 ng for 1 slice(4 μm)and more than 400 ng for 5 slices.Conclusion The DNA purification nanomagnetic beads screened with DNA from FFPE samples have a significant enhancement comparing to the existing commercial bead proto-cols,and provide space for quality assurance,automated testing,and program expansion for clinical molecular pathology testing.
10.Shaping global health promotion:a comprehensive analysis of the 10 Global Conferences on Health Promotion Conferences(1986-2021)
Liu SHIYU ; Sun MEICHEN ; Zhang NA ; Sun ZHAOZHANG ; Tian XIANGYANG ; Li LIMING ; Wang YOUFA
Global Health Journal 2024;8(2):91-96
Objective:This study analyzed how the 10 Global Conferences on Health Promotion have played a significant role in shaping and promoting a worldwide consensus and actions on health promotion,effectively addressing diverse health challenges that evolved over different periods. Methods:The textual analysis method was used in this study and text encoding was conducted to systematically examine the declarations and reports presented by the 10 Global Conferences on Health Promotion held during 1986-2021.We summarized the themes and key achievements,and key vocabulary in the conference declarations was extracted and analyzed to construct the global health promotion consensus and actions. Results:The fundamental principles of the conferences are to foster consensus and initiate actions in the realm of health promotion on a global scale.The primary purpose and goal are to promote health from regional to global.Significantly,our findings highlight a transition in the primary actors driving health promotion.It underscores a shift in health promotion from being driven primarily by organizations like the World Health Organization,governments,and international bodies,to a more inclusive approach involving non-governmental organizations and the general public.This development implies that health promotion has evolved into a collective global en-deavor,demanding the proactive involvement of various stakeholders,and forging new alliances in public health.Meanwhile,the coronavirus disease 2019(COVID-19)pandemic has further shaped the landscape of health pro-motion,underscoring the need for intensified focus on areas including disease prevention,health education,and the integration of digital health technologies,and emphasizing the importance of a multidimensional,responsive approach in public health initiatives. Conclusions:Sustained collaboration and innovative strategies are pivotal to advancing health promotion globally.Countries,together with public and private entities,should intensify cooperation.Multisectoral collaboration among partners such as healthcare,education,social security,and the industry is vital for health promotion and achieving global health goals.


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