1.Molecular Crosstalk Mechanisms of Shoutai Wan and Juyuan Jian on Maternal-fetal Interface Subcellular Clusters in CBA/J×DBA/2 Recurrent Pregnancy Loss Model
Jingxin GAO ; Qiuping CHEN ; Xiaoyan ZHENG ; Pengfei ZENG ; Rui ZHOU ; Yancai TANG ; Qian ZENG ; Wenli GUO ; Jinzhu HUANG ; Weijun DING ; Linwen DENG ; Hang ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):70-87
ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss (RPL) by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus (Shoutai Wan, Juyuan Jian)-of traditional Chinese medicine (TCM) at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c (blank group) and DBA/2 (modeling group) mice separately. Pregnant mice in the modeling group were randomly grouped as follows: high/low-dose Shoutai Wan, high/low-dose Juyuan Jian, model (RPL), and positive control (dydrogesterone), with 10 mice in each group. Starting from the day after the detection of the vaginal plug, mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention, the following indicators were measured. ① Macroscopic evaluation: general conditions, uterine wet weight, embryo loss rate, four coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT)], and peripheral blood estradiol (E2) and progesterone (Pg) levels. The decidua with embryos was stained with hematoxylin-eosin (HE) and evaluated by transmission electron microscopy (TEM). The expression of B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), angiotensin Ⅱ (AngⅡ), matrix metalloproteinase-2 (MMP-2), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), CXC chemokine ligand 12 (CXCL12), and microtubule-associated protein 1 light chain 3 homolog (LC3)Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level: The decidua with embryos from the blank, model, high-dose Shoutai Wan, and high-dose Juyuan Jian groups (6 mice per group, with 3 single-cell samples per group, totaling 24 mice) were analyzed by the BD Rhapsody™ platform, and the whole-cell atlas was drawn by uniform manifold approximation and projection (UMAP) dimensionality reduction clustering combined with the single-cell mouse cell atlas (scMCA). The differentially expressed genes (DEGs) and cell interaction networks were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat, and the protein-protein interaction (PPI) map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells (natural killer cells, NK cells) from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group, the RPL group showed an increase in the embryo loss rate (P<0.01), down-regulated expression of Bcl-2, LIF, MMP-2, and Vegf in the decidua with embryos (P<0.05), up-regulated protein levels of CXCL-12, AngⅡ, and IL-6 (P<0.05), blocked angiogenesis, apoptosis-inflammation imbalance, and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance, and Shoutai pill showed superior performance in restoring the E2 level to the Pg level (P<0.05). ② Single-cell transcriptome analysis indicated that compared with the blank group, the RPL group showed differences in multiple key cell populations such as decidual cells, trophoblast cells, endothelial cells, erythroblasts, NK cells, and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group, high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer (upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes) and macrophages (upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes) through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins, cell adhesion, and programmed cell death, thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells (up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes) and macrophages (up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes), which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D, CDH5, GDF, and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 (STAT3) and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis (TWEAK) signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7, a decreased proportion of reparative dNK4, and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1, thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method (Shoutai Wan) has an advantage in regulating the phenotypes of unfolded protein, cell adhesion, and programmed cell death, and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method (Juyuan Jian) has an advantage in regulating epithelial-mesenchymal transition (EMT), angiogenesis, and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.
2.HAN Mingxiang's Experience in Clinical Application of Zeqi (Euphorbia HelioscopiaL.)
Jian DING ; Weizhen GUO ; Jiabing TONG ; Zegeng LI ;
Journal of Traditional Chinese Medicine 2025;66(4):340-343
This paper summarizes Professor HAN Mingxiang's clinical experience in the use of Zeqi (Euphorbia HelioscopiaL.). It is believed that Zeqi (Euphorbia HelioscopiaL.) has the effects of promoting qi, relieving water retention and swelling, resolving phlegm, stopping cough, dissipating masses, activating blood, removing stasis, and detoxifying. In clinical practice, Zeqi (Euphorbia HelioscopiaL.) is flexibly applied in the treatment of skin diseases, respiratory diseases, tumors, etc. For instance, in treating psoriasis with the pathogenesis of damp-heat toxin, a compound prescription of Zeqi Decoction (泽漆汤) is formulated. For bronchial asthma with kidney deficiency and water retention, Zeqi Decoction is commonly combined with Wuling Powder (五苓散) in adjusted doses. For lung nodules with a combination of deficiency, phlegm, stasis, and toxin, a Lung Nodule Prescription is proposed. For advanced lung cancer with both qi and yin deficiency and toxin accumulation, Qiyu Sanlong Decoction (芪玉三龙汤) is suggested, and for cancer-related ascites with qi deficiency and water retention, Wuling Powder combined with Zeqi (Euphorbia HelioscopiaL.)is chosen.
3.Prognostic Factors of Liposarcoma in Head and Neck
Shuo DING ; Zhigang HUANG ; Jugao FANG ; Yang ZHANG ; Lizhen HOU ; Wei GUO ; Gaofei YIN ; Qi ZHONG
Cancer Research on Prevention and Treatment 2025;52(1):31-35
Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.
4.Review on separation and determination of 63Ni in solid wastes and liquid effluents from nuclear power plants
Mengyu FU ; Xinjie GUO ; Xuqin ZHANG ; Junwu TANG ; Yongshi XU ; Hongshen DING
Chinese Journal of Radiological Health 2025;34(1):142-148
63Ni is predominantly generated through neutron activation in nuclear reactors and is classified as a pure beta-emitting radionuclide with a half-life of 101.1 a. During decay, 63Ni emits a beta ray with an energy of 65.87 keV. 63Ni can be used in the manufacture of beta radiation sources, which are utilized as reference and working sources for beta activity measurement and beta energy response calibration. Additionally, it is used in electron capture detectors for chromatography, ionization sources in electron tubes, and electron capture probes in gas chromatography. These instruments have extensive applications in food safety, public health and epidemic prevention, soil pollution monitoring, and security. 63Ni is an artificial radionuclide not commonly found in the natural environment under normal conditions. However, the 63Ni generated during routine operations of nuclear power plants, as well as residual materials and wastes contaminated with 63Ni during plant decommissioning, may be released into the environment through liquid effluents or solid wastes. This can pose potential radiation risks to both the public and the environment. Hence, it is necessary to monitor the activity concentration of 63Ni. Currently, reports on this subject are limited in China, and there is a lack of established standards for the determination of 63Ni in nuclear power plants. This article reviews the global literature on the pretreatment and purification measurement processes of 63Ni. The merits and demerits are summarized for pretreatment methods such as acid leaching, mixed acid digestion, ashing acid leaching/dissolution, and alkali fusion, and for separation and purification methods like solvent extraction, precipitation, and extraction chromatography. The article also highlights the advantages of measurement using liquid scintillation counters. This review provides a reference for the establishment of the determination method of 63Ni in liquid effluents and solid wastes from nuclear power plants.
5.HAN Mingxiang's Experience in Staged and Syndrome-Based Treatment of Chronic Obstructive Pulmonary Disease
Jian DING ; Hui TAO ; Gang CHENG ; Weizhen GUO ; Zegeng LI ; Ya MAO ;
Journal of Traditional Chinese Medicine 2025;66(8):780-785
This paper summarizes Professor HAN Mingxiang's clinical experience in treating chronic obstructive pulmonary disease (COPD). He believes that the key pathomechanism of COPD in the acute exacerbation stage is the invasion of external pathogens triggering latent illness, while lung qi deficiency is the primary mechanism in the stable stage. The core pathological factors throughout disease progression are deficiency, phlegm, and blood stasis. Treatment emphasizes a staged and syndrome-based approach. During the acute exacerbation stage, for wind-cold invading the lung syndrome, the self-formulated Sanzi Wenfei Decoction (三子温肺汤) is used to relieve the exterior, dispel cold, warm the lung, and resolve phlegm. For phlegm-dampness obstructing the lung syndrome, Huatan Jiangqi Fomulation (化痰降气方) is prescribed to warm the lung, transform phlegm, descend qi, and calm wheezing. For phlegm-heat obstructing the lung syndrome, Qingfei Huatan Fomulation (清肺化痰方) is applied to clear heat, resolve phlegm, moisten the lung, and stop coughing. For phlegm and blood stasis interlocking syndrome, Qibai Pingfei Fomulation (芪白平肺方) is used to tonify qi, resolve phlegm, and activate blood circulation to remove stasis. During the stable stage, for lung qi deficiency syndrome, Shenqi Wenfei Decoction (参芪温肺汤) is employed to warm the lung, tonify qi, resolve phlegm, and eliminate turbidity. For lung-spleen qi deficiency syndrome, Shenqi Buzhong Decoction (参芪补中汤) is utilized to strengthen the spleen, tonify qi, and reinforce metal (lung) from earth (spleen). For lung-kidney deficiency syndrome, Shenqi Tiaoshen Fomulation (参芪调肾方) is prescribed to tonify the lung, warm yang, and regulate kidney function to calm wheezing. These strategies provide insights into the traditional Chinese medicine treatment of COPD.
6.Treatment of Recurrent Pediatric Cough and Asthma Based on the Theory of "Mutual Dependence of Ascending and Descending" from the Perspectives of Deficiency,Phlegm,and Blood Stasis
Yu LIU ; Ying DING ; Yongbin YAN ; Xuran GUO ; Linlin LIU
Journal of Traditional Chinese Medicine 2025;66(9):963-967
Guided by the theory of "mutual dependence of ascending and descending", recurrent pediatric cough and asthma are considered to result from the imbalance of the ascending and descending of zang-fu organ qi, which is closely associated with deficiency, phlegm, and blood stasis. In clinical practice, the disease is treated based on differentiation during the initial stage, progression stage, and stable stage. In the initial stage, the pathogenesis is attributed to lung deficiency complicated by external pathogens and liver qi rising to attack the lung; the treatment should focus on restraining the lung and calming the liver, using the self-formulated Longchai Yuchuan Fomulation (龙柴愈喘方). During the progression stage, the disorder is due to the spleen failing to ascend clear qi and the kidney failing to grasp qi, leading to phlegm formation from deficiency; treatment should focus on tonifying spleen yang, supplementing kidney qi, and resolving phlegm and fluid retention, using a modified combination of Linggui Zhugan Decoction (苓桂术甘汤) and Jinkui Shenqi Pill (金匮肾气丸). In the stable stage, qi deficiency leads to poor consolidation, with phlegm turbidity and blood stasis; the treatment should aim at tonifying qi, transforming phlegm, and dispelling blood stasis, using a modified version of Guizhi Fuling Pill (桂枝茯苓丸).
7.Regulation of mesenchymal stem cell-derived exosomes on helper T cells in periodontitis
WEN Yuqi ; GUO Shujuan ; DING Yi
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(5):409-416
T helper cells (Th cells) play an important role in periodontitis. During the progression of periodontitis, the levels of pro-inflammatory cytokines such as INF-γ and IL-17, which are produced by Th1 and Th17 cells, are elevated, while the levels of anti-inflammatory cytokines such as IL-4 and TGF-β, which are secreted by Th2 cells and regulatory T cells (Tregs), are diminished. Interventions using mesenchymal stem cells (MSCs) or their exosomes can alter the dynamics of helper T cell populations and their associated cytokine profiles, thereby mitigating the bone loss associated with periodontitis or even promoting bone regeneration. Mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to directly modulate Th cell activity through the proteins and microRNAs they transport. Recent studies indicate that MSC-exos carry immune-suppressive protein molecules: PD-L1 and IDO contribute to regulating the balance between Th17 and Tregs; TGF-β inhibits the proliferation of T lymphocytes while facilitating differentiation into Tregs by sustaining forkhead box protein O3 (FOXP3) and Smad expression; and CD73 catalyzes the conversion of monophosphate adenosine into adenosine, which interacts with A2A receptors on Th1 cells to induce apoptosis in Th1 cells. In addition, microRNAs exhibit immunoregulatory functions: periodontal ligament stem cell-derived exosomes contain miRNA-155-5p, which targets sirtuin-1 to suppress Th17 cell differentiation. Furthermore, evidence in rat models of periodontitis suggests that these exosomes may also carry miR-205-5p targeting XBP1 to restore the balance between Th17 and Tregs. Dental pulp stem cell-derived exosomes reestablish this balance via the miR-1246/Nfat5 axis. Bone marrow mesenchymal stem cell-derived exosomes harbor miR-1246, which targets ACE2 to promote differentiation towards Tregs. Moreover, MSC-exos can indirectly enhance the differentiation of Tregs through interactions with other immune entities, such as antigen-presenting cells or macrophages. This article reviews the changes and roles of helper T cells in periodontitis, as well as the regulatory role of exosomes on helper T cells, hoping to provide new ideas for immunotherapy in the treatment of periodontitis.
8.Dosimetric comparison of the heart and its substructures between two hybrid radiotherapy plans following breast-conserving surgery for left-sided breast cancer
Lin GUO ; Hongrong REN ; Meng CHEN ; Chengjun WU ; Yun ZHOU ; Xiaobo RUAN ; Ji DING ; Weiyuan WU
Chinese Journal of Radiological Health 2025;34(2):174-178
Objective To compare the dosimetric differences in the heart and its substructures between two hybrid plans for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. Methods A total of 46 patients with early-stage left-sided breast cancer who underwent hypofractionated whole-breast radiotherapy were randomly selected. Two hybrid radiotherapy plans were used, including hybrid intensity-modulated radiotherapy (H_IMRT) and hybrid volumetric-modulated arc therapy (H_VMAT). The heart and its substructures were contoured, including left anterior descending (LAD), left ventricle (LV), right coronary artery (RCA), and right ventricle (RV). The heart and substructure doses, as well as monitor units, were compared between H_IMRT and H_VMAT. Results Both hybrid plans met the clinical requirements. H_IMRT significantly outperformed H_VMAT for the heart (V10, V30, and Dmean), LAD (V30, V40, Dmax and Dmean), LV (V10, V20 and Dmean), RCA (Dmax, Dmean), and RV (V5, V10, Dmean) (P < 0.001). Additionally, H_IMRT was significantly superior to H_VMAT for heart V5, LAD V20, and RV V20 (P = 0.005, 0.035 and 0.037). For LAD (V15, V40) and LV (V5, V25), H_IMRT was slightly better than H_VMAT, and the difference was not statistically significant. Conclusion Both H_IMRT and H_VMAT hybrid radiotherapy plans are suitable for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. H_IMRT is slightly better than H_VMAT in dose sparing for the heart and its substructures.
9.Gradient artificial bone repair scaffold regulates skeletal system tissue repair and regeneration
Yu ZHANG ; Ruian XU ; Lei FANG ; Longfei LI ; Shuyan LIU ; Lingxue DING ; Yuexi WANG ; Ziyan GUO ; Feng TIAN ; Jiajia XUE
Chinese Journal of Tissue Engineering Research 2025;29(4):846-855
BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.
10.miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by regulating mitogen-activated protein kinase signaling pathway
Jun LI ; Jingjing GONG ; Guobin SUN ; Rui GUO ; Yang DING ; Lijuan QIANG ; Xiaoli ZHANG ; Zhanhai FANG
Chinese Journal of Tissue Engineering Research 2025;29(8):1609-1617
BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.


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