1.Hydrogels:role and problems in the repair of oral and maxillofacial defects
Zhixin WU ; Wenwen JIANG ; Jianhui ZHAN ; Yangshurun LI ; Wenyan REN ; Yiyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(10):2178-2188
BACKGROUND:Hydrogels have become a research hotspot due to their unique advantages in the biomedical field due to their superior mechanical and biological properties.At present,related research involves tissue engineering,wound dressing and so on. OBJECTIVE:To review the advantages and properties of hydrogels and the research progress of their application in the repair of oral and maxillofacial defects,discuss the current limitations and challenges of hydrogels in application and promotion,and provide new ideas for future research directions. METHODS:Relevant literature was searched in PubMed,CNKI,and WanFang database by computer.The search terms were"hydrogel,oral and maxillofacial defects,mechanical properties,tissue engineering,wound dressing"in Chinese and"hydrogel,oral and maxillofacial defects,mechanical properties,guided tissue regeneration,wound dressing"in English.Preliminary screening was carried out by reading titles and abstracts,and articles not related to the topic of the article were excluded.According to the inclusion and exclusion criteria,108 articles were finally included for the result analysis. RESULTS AND CONCLUSION:(1)The hydrogel has good biological activity,mechanical controllability,and stimulation response.(2)Polymer,metal,and ceramic hydrogel composites have appropriate mechanical properties,biodegradability,and controlled release rate,which are suitable for maxillofacial bone tissue engineering.(3)Fibrin-based hydrogel could fill the hollow nerve conduit through the nerve defect area and promote the regeneration and growth of axons to restore the function of maxillofacial nerve.(4)Controlling the interaction between nanomaterials and hydrogels can improve the formation of muscle fiber oriented structure to promote maxillofacial muscle tissue regeneration.(5)Polysaccharide hydrogel has gradually become the first choice for repairing irregular periodontal defects due to its ability to control drug delivery,carry bioactive molecules,and combine with other materials to produce the best scaffold matching the extracellular matrix.(6)Calcium phosphate or calcium carbonate-based hydrogels can be used to fill irregular or fine tissue defects and remineralize hard tissues.The self-assembled hydrogels are simple to prepare and have good biological activity.(7)Salivary gland-derived extracellular matrix-like gel is expected to participate in the treatment of many salivary gland diseases.(8)Hydrogels can be used as wound dressings in combination with biological adhesives,acellular biomaterials,antimicrobials,antioxidants,or stem cells to treat various wounds.(9)Fibrin-based hydrogel has the most potential in the repair of oral and maxillofacial defects.It has excellent biocompatibility,flexibility,and plasticity.It can combine with cells,extracellular matrix proteins,and various growth factors,and promote the osteogenic differentiation of mesenchymal stem cells,axon regeneration and growth,angiogenesis,myotube differentiation,salivary gland tissue regeneration,and periodontal tissue regeneration.It has a broad prospect in the repair of oral and maxillofacial defects.However,its therapeutic effect depends on the function of the substance carried.The complex preparation process,its safety and long-term efficacy,and the special anatomical oral and maxillofacial structure is the problem that hinders its promotion,which also provides directions for future research.
2.Mechanism by which exogenous basic fibroblast growth factor promotes wound healing in rats
Zhenchao LI ; Xiling DU ; Zhixin HAN ; Dawei NIU ; Changwei FAN
Chinese Journal of Tissue Engineering Research 2025;29(11):2243-2251
BACKGROUND:This study provided insight into the molecular mechanisms by which exogenous basic fibroblast growth factor(bFGF)promotes wound healing. OBJECTIVE:To investigate the effect of exogenous bFGF on macrophage phenotype transition and granulation regeneration during wound repair in rats. METHODS:(1)In vitro experiment:Cells were divided into normal control group,low-dose bFGF group,high-dose bFGF group,and bFGF+valproic acid group.100 and 200 μg/L bFGF was added into the cell culture medium of low-dose bFGF group and high-dose bFGF group,respectively,while 200 μg/L bFGF and 20 mmol/L valproic acid were added into the cell culture medium of valproic acid group.EdU test,scratch test and tubule formation test were used to detect the effects of bFGF on proliferation,migration and angiogenesis of human umbilical vein endothelial cells.(2)In vivo experiment:Sprague-Dawley rats were randomly divided into model group,low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.The open wound model of full-thickness skin defect was established in low-dose bFGF group,high-dose bFGF group and bFGF+valproic acid group.Rats in the low-and high-dose bFGF groups were given 100 and 200 μg/L bFGF through subcutaneous injection,while those in the bFGF+valproic acid group received subcutaneous injection of 200 μg/L bFGF and intraperitoneal injection of 10 mg/kg valproic acid.The wound healing rate of rats was detected at 7 and 14 days of administration.TUNEL was used to detect the apoptosis of cells in wound tissue.Enzyme linked immunosorbent assay was used to detect the serum levels of malondialdehyde,superoxide dismutase,tumor necrosis factor-α and interleukin-10.Immunofluorescence detection was conducted to detect the phenotypic transformation of macrophages in wound tissue.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen,platelet endothelial cell adhesion molecule-1(CD31)and vascular endothelial growth factor in wound tissue.Western blot was used to detect the expression of Notch1 and Jagged1 in wound tissue. RESULTS AND CONCLUSION:(1)Compared with the normal control group,bFGF could significantly promote the proliferation,migration and angiogenesis of human umbilical vein endothelial cells in a dose-dependent manner.(2)Compared with the model group,bFGF could significantly promote wound healing,downregulate the rate of apoptosis in wound tissue,decrease the levels of malondialdehyde and tumor necrosis factor-α in serum,increase the levels of superoxide dismutase and interleukin-10,promote the conversion of macrophages to type M2 in wound tissue,upregulate the expression of proliferating cell nuclear antigen,CD31 and vascular endothelial growth factor in wound tissue,and inhibit the expression of Notch1 and Jagged1 in a dose-dependent manner.Valproic acid could partially reverse the promoting effect of bFGF on wound healing.To conclude,bFGF can significantly promote wound healing and granulation regeneration and induce the conversion of macrophages to M2,which may be related to the regulation of Notch1/Jagged1 signaling pathway.
3.Inhibitory Effects of the Slit Guidance Ligand 1-3’ Untranslated Region on the Fibrotic Phenotype of Cardiac Fibroblasts
Ya WANG ; Huayan WU ; Yuan GAO ; Rushi WU ; Peiying GUAN ; Hui LI ; Juntao FANG ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):466-474
ObjectiveTo study the regulatory effect of the partial sequence within the 3’ untranslated region (3’UTR) of slit guidance ligand 1 (Slit1) (Slit1-3’UTR) on the fibrotic phenotypes of cardiac fibroblasts (CFs) and its potential mechanism. MethodsThe adenovirus vector was used to overexpress the 1526nt sequence of Slit1-3’UTR in ICR neonatal mouse CFs (mCFs). The expression of fibrosis-related genes in mCFs, such as collagen type 1 alpha1(COL1A1), collagen type 3 alpha3 (COL3A1) and alpha smooth muscle actin (α-SMA) were detected by Western blot assay. The effect of Slit1-3’UTR 1526nt on the proliferation and migration of mCFs was assessed by EdU staining and Trans-well assays. Angiotensin Ⅱ (Ang Ⅱ) was used to treat mCFs, and the impact of Slit1-3’UTR 1526nt on the fibrotic phenotypes of Ang Ⅱ-induced mCFs was evaluated. After overexpression of Slit1-3’UTR 1526nt, miR-34a-5p mimic was transfected into mCFs, followed by actinomycin D treatment to detect the mRNA stability of Slit1-3’UTR 1526nt, and the levels of miR-34a-5p and its target gene SIRT1(si-SIRT1) in mCFs were determined. The effects of miR-34a-5p and small interfering RNA targeting SIRT1 on the Slit1-3’UTR 1526nt-mediated regulation of fibrotic phenotypes were also determined. ResultsAdenovirus-mediated overexpression of Slit 1-3’UTR 1526nt was achieved in mCFs. Overexpression of Slit 1-3’UTR 1526nt markedly inhibited the expression of the fibrosis-related genes, proliferation and migration of mCFs and fibrotic phenotypes of Ang Ⅱ. The results of actinomycin D assay showed that miR-34a-5p inhibited the stability of Slit1-3’UTR 1526nt in mCFs, while the level of miR-34a-5p was reduced in mCFs with overexpression of Slit1-3’UTR 1526nt. Transfection of miR-34a-5p promoted the fibrotic phenotypes, and reversed the inhibitory effect of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. Overexpression of Slit1-3’UTR 1526nt significantly increased the level of miR-34a-5p target gene SIRT1 in mCFs. Transfection of miR-34a-5p and si-SIRT1 consistently reversed the inhibitory effects of Slit1-3’UTR 1526nt on the fibrotic phenotypes of mCFs. ConclusionSlit1-3’UTR1526nt inhibits the fibrotic phenotypes of mCFs by binding to miR-34a-5p and increasing the expression of its target gene of SIRT1.
4.IDH3A Inhibits Cardiomyocyte Hypertrophy via Elevating α-Ketoglutarate Level
Huayan WU ; Yihong WEN ; Hengli ZHAO ; Yuan GAO ; Chuanmeng ZHOU ; Ya WANG ; Jiening ZHU ; Zhixin SHAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):275-283
ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A (IDH3A) on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers (n=10) and patients with heart failure (HF) (n=10), and in the myocardium of mice subjected to transverse aortic constriction (TAC) surgery and sham operation, as well as in phenylephrine (PE)-induced neonatal rat ventricular cardiomyocytes (NRVCs), was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity, IDH3A_D208A, was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype, ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid (AKG) on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay, respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients, in the myocardium of TAC-operated mice, and in PE-induced NRVCs (P = 0.005 2,P = 0.026 6,P = 0.041 3 and P = 0.006 6, respectively). Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs (P < 0.000 1, P = 0.000 1 and P = 0.000 2, respectively). The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs (P = 0.001 2 and P<0.000 1, respectively), whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could, but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level, providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.
5.Research progress on the treatment of ischemia-reperfusion injury with human umbilical cord mesenchymal stem cells and their derivatives
Ru NIE ; Yunlong DUAN ; Mingquan PANG ; Zhixin WANG ; Haining FAN
Organ Transplantation 2025;16(4):516-525
Ischemia-reperfusion injury (IRI) can lead to organ dysfunction and tissue necrosis in the liver, kidney, myocardium and spinal cord, and there is currently a lack of effective treatment options. Human umbilical cord mesenchymal stem cell (HUC-MSC) and their derivatives have anti-inflammatory, anti-apoptotic, reactive oxygen species scavenging, mitochondrial and endothelial function improvement properties, and are ideal gene therapy carrier cells, providing new possibilities for the treatment of IRI in different organs. This article reviews the concept and mechanisms of IRI, the biological characteristics of HUC-MSC and their derivatives and their comparison with mesenchymal stem cells from other sources, and the mechanisms of HUC-MSC in treating IRI in different organs. It also summarizes and analyzes the advantages and disadvantages of HUC-MSC in protecting different organs from IRI, and prospects future research directions to explore more valuable research paths.
6.Efficacy and Safety of Acupuncture Combined with Levodopa in the Treatment of Parkinson's Disease: A Randomized Controlled Trial
Jingyun ZHU ; Xiyan GAO ; Linlin WANG ; Zhixin REN ; Guiling WANG ; Jing GUO ; Yanrong WU
Journal of Traditional Chinese Medicine 2025;66(14):1456-1462
ObjectiveTo evaluate the clinical efficacy and safety of acupuncture combined with levodopa in the treatment of Parkinson's disease(PD). MethodsA total of 60 patients with PD were enrolled and randomly assigned to test group or control group, with 30 patients in each group. The control group received levodopa only, starting at 100 mg per dose, three times daily, with gradual increases not exceeding a maximum daily dose of 800 mg. The test group received acupuncture three times per week in addition to levodopa. Both groups were treated for 12 weeks. Assessments were conducted before treatment, after 6 and 12 weeks treatment, using the Unified Parkinson's Disease Rating Scale(UPDRS), Wearing-Off Questionnaire-9(WOQ-9), Montreal Cognitive Assessment(MoCA), Mini-Mental State Examination(MMSE), Depression Rating Scale(DRS), Hamilton Depression Scale(HAMD), Hamilton Anxiety Scale(HAMA), PD Questionnaire-39(PDQ-39), and Pittsburgh Sleep Quality Index(PSQI). Repeated measures ANOVA was utilized to evaluate the effects of time, group, and their interaction on each index. Spearman correlation analysis was conducted to examine the relationships between combined treatment and outcome scores. Adverse events in both groups were recorded throughout the study. ResultsBoth groups showed significant improvements after 6 and 12 weeks treatment, with decreases in UPDRS total score, WOQ-9 total score, DRS score, HAMD score, HAMA score, PDQ-39 score, and PSQI score, and increases in MoCA and MMSE scores(P<0.05). Compared with the control group, the test group demonstrated significantly greater improvements in all the above indicators after 6 and 12 weeks (P<0.05). Repeated measures ANOVA showed significant time main effects, group main effects, and their interaction across all outcome measures(P<0.01). Spearman correlation analysis revealed that combined therapy was significantly negatively correlated with UPDRS, WOQ-9, DRS, HAMD, HAMA, PDQ-39, and PSQI scores, while positively correlated with MoCA and MMSE scores after 12 weeks of treatment(P<0.05). Both groups did not experience any serious adverse events and did not affect treatment. ConclusionAcupuncture combined with levodopa is more effective than levodopa alone in improving motor function, non-motor symptoms, cognitive function, depression and anxiety, quality of life, and sleep quality in patients with PD, with good safety.
7.Research progress of Faricimab in the treatment of macular edema associated with retinal vascular diseases
Xinyi HOU ; Haoran WANG ; Chunhua DAI ; Jing ZHANG ; Meng XIN ; Zhixin GUAN ; Shu LIU
International Eye Science 2025;25(8):1267-1273
Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.
8.Evaluation of the effect of campus tray design on salt intake control among boarding students in Guizhou Province
QIU Yujie, DU Zhixin, YUAN Fan, ZHAO Hang, LIU Ailing
Chinese Journal of School Health 2025;46(7):956-960
Objective:
To explore the effect of replacing rice bowls with trays on controlling the salt intake among school aged children, providing new evidence and insights for salt reduction intervention.
Methods:
From April to May 2024, 373 students from grades 4-9 at a boarding school in Guizhou Province were enrolled through stratified random cluster sampling, with one intervention class and one control class per grade. During the intervention period for one month, and the types of meals provided, pricing standards, and dining procedures shall remain consistent with daily operations, the intervention group ( n =181) compartmentalized trays for lunch and dinner, while the control group ( n =192) still used a rice bowl. Pre and post intervention assessments included 24 hour urine collection, questionnaire surveys, and physical measurements. The difference in differences analysis combined with multiple linear regression was used to analyze the changes in sodium intake and to evaluate the net effect of the intervention.
Results:
The post intervention 24 hour sodium intake in the intervention group was ( 2 222.6 ±1 013.6) mg, an increase of 94.6 mg from baseline, with no statistically significant difference ( t=1.10, P >0.05). In contrast, the post intervention 24 hour sodium intake in the control group was (2 080.5±895.7) mg, a decrease of 190.8 mg from baseline, showing a statistically significant difference ( t=-2.39, P <0.05). The difference in differences results indicated that after adjusting the model for factors such as gender, grade and dietary behaviors affecting sodium intake, the intervention group showed a net increase of 232.5 mg [ β(95%CI )=232.5(-40.3-505.2)] in 24 hour sodium intake compared to the control group, with no statistically significant net effect ( P >0.05).
Conclusions
Merely changing tableware is insufficient to control children s salt intake effectively. Based on continuous practical explorations and evidence based research grounded in the nudge theory, multi dimensional measures such as salt reduction education and the construction of a supportive environment should be integrated to form an intervention system that achieves synergistic and enhanced effects.
9.Anti-tumor Effect and Mechanism of Active Ingredients from Yin-nourishing Chinese Herbs: A Review
Qimeng FAN ; Yanran HE ; Liangshan MING ; Zishu DONG ; Yingjiao LIU ; Zhixin LI ; Jia HUANG ; Hongning LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):252-265
Tumor has become a major disease that seriously threatens human health and life. The incidence rate is increasing year by year, yet the underlying mechanisms remain incompletely understood. Traditional Chinese medicine (TCM), a treasure of the Chinese nation and a wealth for people worldwide, plays an important role in the treatment of tumors and has been receiving increasing attention both in China and abroad. In earlier work, based on the symptoms and metastatic characteristics of tumors, and drawing on the TCM theory of Yin and Yang in combination with modern medical research on tumors, the ''Yin deficiency-cancer correlation'' hypothesis was proposed. This hypothesis holds that ''Yin deficiency'' of the body is a major cause of malignant tumors, and that nourishing Yin to eliminate the pathogenic factor of Yin deficiency can treat cancer. By using Yin-nourishing drugs to tonify Yin deficiency, the occurrence and development of malignant tumors can be effectively prevented. Common anti-tumor Yin-nourishing drugs include Glehniae Radix, Lilii Bulbus, Ophiopogonis Radix, Liriopes Radix, Asparagi Radix, Dendrobii Caulis, Dendrobii Officinalis Caulis, Polygonati Odorati Rhizoma, Polygonati Rhizoma, Lycii Fructus, Mori Fructus, Ligustri Lucidi Fructus, Ecliptae Herba, Rehmanniae Radix, and Anemarrhenae Rhizoma. These drugs are generally sweet in flavor, cold and cool in nature, and moist in texture. They have the functions of nourishing Yin fluids, generating body fluids, and moistening dryness, and can also clear heat, being primarily indicated for Yin deficiency with depletion of body fluids. In view of the potential advantages and value of treating malignant tumors by tonifying Yin deficiency with Chinese medicine, this paper reviews recent studies on the anti-tumor effects of active components of Yin-nourishing drugs. It further summarizes their mechanisms of action in inducing apoptosis of tumor cells, arresting tumor cell proliferation, inhibiting tumor invasion, metastasis, and angiogenesis, enhancing and regulating immune function, augmenting the efficacy of chemotherapeutic drugs, and reversing tumor drug resistance. This study provides an objective overview of research progress on Yin-nourishing drugs in tumor treatment and offers new ideas for cancer therapy.
10.A Case Report of Jansen-de Vries Syndrome Caused by PPM1D Gene Mutation and Literature Review
Mei XUE ; Bo PANG ; Xiaoqian ZHANG ; Ziyu GAO ; Bo ZHOU ; Zhixin ZHANG
JOURNAL OF RARE DISEASES 2025;4(3):355-360
Jansen-de Vries syndrome, also known as intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, is a rare autosomal dominant disorder characterized by multisystem involvement. This article reports the case of a young child who presented with global developmental delay, gastrointestinal dysfunction, intellectual disability, and short stature. Distinct facial features included a broad forehead, low nasal bridge, thin upper lip, and widely spaced and misaligned teeth. Additional phenotypic findings involved small hands and feet, as well as digital anomalies. Through whole-exome sequencing (WES) and copy number variation (CNV) analysis, a pathogenic variant was identified in the


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