1.Fibroblast growth factors and endometrial decidualization: models, mechanisms, and related pathologies.
Xueni ZHANG ; Yidi MO ; Chunbin LU ; Zhijian SU ; Xiaokun LI
Journal of Zhejiang University. Science. B 2025;26(6):573-588
The onset of pregnancy is marked by the formation of a zygote, while the culmination of gestation is manifested by the delivery of a fetus. Meanwhile, a successful pregnancy entails a meticulously coordinated sequence of events from embryo implantation to sustained decidualization of the uterus to placental development and childbirth. The decidual reaction, a pivotal process occurring within the endometrium during pregnancy, is finely regulated by sex steroids and cytokines. Notably, fibroblast growth factors (FGFs), particularly FGF2, play a critical role in this physiological cascade. Dysregulated FGF expression may trigger inadequate decidualization, precipitating a spectrum of adverse pregnancy outcomes, including preeclampsia, recurrent implantation failure, and miscarriage. Furthermore, the human decidua, distinct from most mammalian species and similar to great apes, undergoes regular cycles of formation and shedding, independent of the presence of the embryo in the endometrium. This process is also tightly controlled by various FGFs. In this review, we comprehensively compare diverse research decidualization models, delineate the trend of endometrial FGFs during the menstrual cycle, and provide a synopsis of endometrial diseases triggered by FGF dysregulation.
Humans
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Female
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Pregnancy
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Decidua/physiology*
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Animals
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Endometrium/physiology*
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Fibroblast Growth Factors/metabolism*
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Embryo Implantation
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Menstrual Cycle/physiology*
2.Evidence that metformin promotes fibrosis resolution via activating alveolar epithelial stem cells and FGFR2b signaling.
Yuqing LV ; Yanxia ZHANG ; Xueli GUO ; Baiqi HE ; Haibo XU ; Ming XU ; Lihui ZOU ; Handeng LYU ; Jin WU ; Pingping ZENG ; Saverio BELLUSCI ; Xuru JIN ; Chengshui CHEN ; Young-Chang CHO ; Xiaokun LI ; Jin-San ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4711-4729
Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.
3.Research on quality evaluation and improvement of in vitro diagnostic reagent supply chain based on zero inventory target
Han WU ; Zhiyong XU ; Xiaokun GAO ; Wenjun GE ; Xianli MA ; Wei DING ; Weizheng LI
China Medical Equipment 2024;21(2):127-131,161
Objective:To establish the objective of zero inventory management of in vitro diagnostic reagents,to evaluate the quality of supply chain,and to improve the existing problems in the supply of reagents.Methods:The problems existing in the management of in vitro diagnostic reagents were analyzed from the aspects of inventory,supply efficiency and product quality,and the management system of hospital operation,management quality and patient benefit optimization was established,and the zero-inventory management path and quality evaluation model were constructed.85 models of 21 types of in vitro diagnostic reagents purchased by Jiangsu Subei People's Hospital from January 2020 to March 2023 were selected.According to different supply chain quality management methods,on-demand inventory management mode(referred to as mode 1)and zero inventory management mode(referred to as mode 2)were adopted respectively.The demand procurement,inventory management and clinical use effects of the two management modes were compared.Results:The reagent procurement demand compliance rate,supply capacity high-quality quality rate and clinical use matching rate of mode 2 were(93.35±3.62)%,(94.87±2.63)% and(96.08±2.31)%,respectively,which were higher than those of mode 1,the difference was statistically significant(Z=2.489,2.836,2.838,P<0.05).The number of cases of long-term overstocking of products,substandard environment and untimely information in mode 2 were(2.92±2.54)cases,(2.83±1.59)cases and(5.58±3.12)cases,respectively,which were lower than those in mode 1,the difference was statistically significant(Z=2.959,3.037,3.703,P<0.05).The satisfaction of clinical departments,medical technology departments and procurement center with the supply,distribution and information communication of in vitro diagnostic reagents in mode 2 were 97.8% and 93.3%,97.0% and 87.9%,100% and 84.6%,respectively,which were higher than those in mode 1,the difference was statistically significant(x2clinical departments=5.428,6.133,x2medical technology departments=3.958,3.937,x2procurement center=5.159,4.996,P<0.05).Conclusion:The zero inventory management model can improve the standardization of in vitro diagnostic reagent demand procurement,reduce the incidence of backlog failure in inventory management,and improve the quality of clinical supply services.
4.Value of Three-dimensional Rectal Intraluminal Ultrasound Combined with Couplant Contrast for Surgical Guidance of Perianal Necrotising Fasciitis
Linghua LI ; Xu HAN ; Xueqin ZHANG ; Xiaokun HUA ; Chunling LI
Journal of Kunming Medical University 2024;45(3):146-150
Objective To explore the application value of Three-Dimensional rectal cavity ultrasound combined with contrast agent imaging in necrotizing fasciitis of the anal region.Methods Before surgery,standard three-dimensional rectal cavity ultrasound examinations(referred to as the conventional group)and contrast agent imaging examinations(referred to as the imaging group)were conducted for 40 patients clinically diagnosed with anal region necrotizing fasciitis.Separate observations were made for the primary lesion,as well as for the depth and superficial necrosis of the fascia,and injuries to the anal sphincter muscle.Comparative analysis with surgical results was undertaken to assess the diagnostic sensitivity of both the conventional and imaging groups.Results In comparing the conventional group with the imaging group,the rates of primary lesion visibility rose significantly from 70%to 97.5%,deep fascial necrosis visibility increased from 50%to 88.8%,superficial fascia visibility improved from 70%to 100%,and the visibility of anal sphincter muscle injury escalated from 62.5%to 97.2%,all demonstrating statistical significance at P<0.05.Conclusions Three-dimensional rectal cavity ultrasound combined with contrast agent imaging exhibits significantly enhanced accuracy in identifying primary lesions associated with perianal necrotizing fasciitis,as well as the necrosis affecting deep and superficial fascia,in contrast to conventional three-dimensional rectal cavity ultrasound.This advancement offers more precise guidance for clinicians in devising surgical plans,thereby augmenting the success rate of surgical interventions.
5.Factors Influencing Inpatient Costs for Patients Undergoing Surgery for Intrauterine Lesions under DRG Payment
Yutong WANG ; Weiguo ZHU ; Xueqin SUN ; Jiali TONG ; Jingya ZHOU ; Qing ZHAO ; Bocheng LI ; Wei ZHANG ; Xiaokun LIU ; Rui DONG ; Chen XIE ; Ding HAN
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1069-1076
To analyze the factors affecting the cost of hospitalization for patients and provide insights using the intrauterine lesion surgery group (DRG code NE19) as an example. This study was a retrospective cross-sectional study, with data from the first page of medical records of patients enrolled under NE19 at a comprehensive tertiary hospital in Beijing from March 15, 2022 to November 30, 2023. Influence factor selection and multifactorial linear regression analysis were conducted with hospitalization cost as the dependent variable, and patient's basic information, treatment information and key concern factors as independent variables. The profit and loss of medical records containing key factors and differences in indicators of hospitalization cost structure were analyzed in the context of clinical practice. A total of 2213 valid medical records (all female patients) were included, with patients predominantly young and middle-aged women under 45 years of age (72.12%), and with 931 day surgery medical records (42.07%). The diagnosis records included 334(15.09%) multiple uterine leiomyomas, and 246(11.12%) pelvic adhesions. A total of 150(6.78%) medical records involved ovary- and tubal-related surgeries or manipulations, with 160(7.23%) main operations being laparoscopic hysterectomy of diseased uterine lesions and 38(1.72%) mechanical rotational excision of abnormal uterine tissue using transhysteroscopy. Linear regression analysis showed that whether or not ovarian and tubal surgical operations were involved ( The NE19 group of hospitals in the study had a high loss rate, and factors such as the severity of the patient's condition and the use of new technologies affected hospitalization costs, suggesting that there is room for further optimization of the existing grouping scheme. Tiered payment standards can be set up for different tiers of healthcare institutions, and a sound and optimized exclusion mechanism can be used to promote the development of new technologies. The internal management of hospitals should encourage the development of daytime surgery to improve the efficiency of medical services.
6.Research progress on safety management of patient handover between operating room and anesthesia recovery room
Junxia XIANG ; Xiaokun LI ; Shaoming DUAN ; Hongwei WANG ; Rong KANG
Chinese Journal of Practical Nursing 2024;40(15):1196-1201
The physiological function of postoperative patients had not returned to normal, coupled with surgical trauma, residual effects of anesthesia and analgesic drugs and potential risk factors, so postoperative patients need to be transferred to the post-anesthesia care unit for observation, until the vital signs were stable before being transferred to the general ward. This paper summarized the importance, safety management status, influencing factors and intervention measures of patient handover between operating room and post-anesthesia care unit, to provide guidance for clinical patient handover and improve the safety of patient handover.
7.Mechanism study of fibroblast growth factors signaling
Zhiqiang HUANG ; Lili FU ; Gaozhi CHEN ; Xiaokun LI
Chinese Journal of Endocrinology and Metabolism 2024;40(10):826-829
This article presents the research design and principal findings of the recent study " Structural basis for FGF hormone signalling" published in Nature. It highlights the study′s significance in elucidating the molecular mechanisms of fibroblast growth factor(FGF)23, FGF receptor(FGFR), Klotho, and heparan sulfate(HS) quaternary complex signalling. These findings offer crucial structural insights that could advance drug discovery for metabolic disorders like diabetes and chronic kidney disease.
8.Research progress of fibroblast growth factor in nervous system diseases.
Wenting HUANG ; Wanhua QIU ; Kun CHEN ; Shasha YE ; Dongxue WANG ; Jian HU ; Huiqin XU ; Li LIN ; Xiaokun LI
Journal of Zhejiang University. Medical sciences 2023;51(6):738-749
Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans
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Fibroblast Growth Factors
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Phosphatidylinositol 3-Kinases/metabolism*
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Central Nervous System/metabolism*
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Signal Transduction/physiology*
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Alzheimer Disease
9.A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy.
Luchen SUN ; Nanfei YANG ; Bing CHEN ; Yuncheng BEI ; Zisheng KANG ; Can ZHANG ; Nan ZHANG ; Peipei XU ; Wei YANG ; Jia WEI ; Jiangqiong KE ; Weijian SUN ; Xiaokun LI ; Pingping SHEN
Acta Pharmaceutica Sinica B 2023;13(7):3027-3042
Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.
10.Constructing a Syndrome Differentiation Model by Combining Latent Structure Analysis of Association Rules: An Example of Kidney Yang Deficiency Syndrome in Primary Osteoporosis
Beibei LI ; Jing WANG ; Xinghua XIANG ; Wenyuan XU ; Weiguo BAI ; Mengyu LIU ; Yukun LI ; Xiaokun WU ; Yongjun WANG ; Wei YANG
Journal of Traditional Chinese Medicine 2023;64(24):2522-2531
ObjectiveTo construct a quantitative differentiation model of traditional Chinese medicine (TCM) syndromes by taking primary osteoporosis (POP) with kidney yang deficiency syndrome as an example, and to provide methodological reference for the standardization of syndrome differentiation. MethodsHigh-frequency clinical features of POP were screened by descriptive statistical analysis, and strong association features of POP were obtained by association rule algorithm. On this basis, a latent structure (latent tree) model was established through latent structure analysis, and the implicit and explicit variables (features) related to POP with kidney yang deficiency syndrome were comprehensively clustered, and the clustering results were interpreted by the indexes of mutual information and cumulative information coverage, to explore the primary and secondary symptoms, and to deduce the categories of POP with kidney yang deficiency syndrome based on the probability of the features appearing in the various latent categories. Based on the categories, the clinical feature scores and identification thresholds were calculated, and the syndrome differentiation model of POP with kidney yang deficiency was initially constructed by combining the comprehensive judgment rules. Finally, the results of TCM professionals' judgment were used as the gold standard to further evaluate the effectiveness of the model in assisting the syndrome differentiation. ResultsThe 32 features strongly associated with POP were obtained, and the Bayes information critedon score of the further constructed latent tree model was -15291.93. Based on the mutual information and the cumulative information coverage, the main symptoms of POP with kidney yang deficiency syndrome were bone weakness, fatigue, pale tongue, clear urine, frequent nocturnal urination, cold limbs, thin pulse, white coating, and secondary symptoms were weakness, loss of libido, loose stool, frequent urination, lumbar and knee weakness, and fear of cold. From the probability of the occurrence of each clinical feature in different latent categories of POP with kidney yang deficiency syndrome, the state was introduced as S0 category (none/mild kidney yang syndrome)/ S1 category (moderate kidney yang syndrome)/ S2 category (severe kidney yang syndrome). Optimizing the preliminary rules of state identification and refining the state of S1 category, the results showed that among 970 patients with POP, there were 520 patients having no/mild kidney yang deficiency syndrome, 224 patients with moderate to mild kidney yang deficiency syndrome, 81 patients with moderate to severe kidney yang deficiency syndrome, and 145 patients with severe kidney yang deficiency syndrome. During the evaluation and validation process, the correct rate of the model assessment index was 0.8835, while the sensitivity was 0.7181, and the specificity was 0.9437. ConclusionCombined with the latent structure analysis of the association rule, the syndrome differentiation model for POP with kidney yang deficiency could be constructed, and the model shows a good quantitative identification effect, which can provide methodological supports for clinicians to improve the efficiency and accuracy of TCM diagnosis.

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