1.Pathogenesis and treatment progress of flap ischemia-reperfusion injury
Bo HE ; Wen CHEN ; Suilu MA ; Zhijun HE ; Yuan SONG ; Jinpeng LI ; Tao LIU ; Xiaotao WEI ; Weiwei WANG ; Jing XIE
Chinese Journal of Tissue Engineering Research 2025;29(6):1230-1238
BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.
2.Clinical Application of Green Prescription of Traditional Chinese Medicine:Problems and Solution Strategies
Yike SONG ; Zhijun BU ; Wenxin MA ; Kai LIU ; Yuyi WANG ; Yuan SUN ; Yang SHEN ; Hongkui LIU ; Jianping LIU ; Zhaolan LIU
Journal of Traditional Chinese Medicine 2025;66(11):1094-1098
Green prescription is a written prescription aimed at improving health by promoting physical activity and improving diet, with advantages such as high cost-effectiveness, strong feasibility, and minimal harm to patients. The theory of traditional Chinese medicine (TCM) green prescription integrates the health philosophy of "following rule of yin and yang, and adjusting ways to cultivating health", the exercise philosophy of balancing yin-yang and the five elements, and the dietary philosophy of moderation and balance, which embody core TCM concepts such as treating disease before its onset and harmony between humans and nature. It has also developed traditional exercise practices like Tai Chi, Baduanjin, Wuqinxi, Yi-Gin-Ching, and Qigong, as well as dietary adjustments like medicated diet and herbal wines. However, it is believed that the TCM green prescription currently suffers from insufficient evidence-based research, low patient awareness and acceptance, and weak basic research. Based on this, it is proposed that large-sample clinical trials should be conducted in the future to improve the quality of evidence-based medicine, basic research can be carried out with the help of artificial intelligence and other methods in research design, the hospital information system (HIS) can be used for control at the implementation level, and publicity and patient education can be strengthened through the new media, so as to promote the development and application of the TCM green prescriptions in the field of global health treatment.
3.Mechanism of Huangqi Gegen Decoction in Treatment of Type 2 Diabetes Mellitus via Intestinal Mucosal Barrier
Lili PENG ; Miao HAO ; Zhijun YANG ; Yajie LIU ; Hongxia YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):1-9
ObjectiveTo investigate the mechanism of Huangqi Gegentang (HGT) in the treatment of type 2 diabetes mellitus (T2DM) through the application of proteomic techniques. MethodsThe rat model of T2DM was established by streptozotocin combined with a high-fat, high-sugar diet. Thirty-two male SD rats were randomized into four groups: blank, model, HGT (8.10 g·kg-1·d-1), and positive control (metformin hydrochloride, 76.5 mg·kg-1·d-1). After 6 weeks of drug intervention, the fasting blood glucose level was measured, and an oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was calculated. Enzyme-linked immunosorbent assay was performed to assess the level of glycated hemoglobin (GHbA1c) in the serum. The limulus amebocyte lysate assay was employed to measure the serum level of lipopolysaccharide (LPS). Pathological changes in the colon were observed by hematoxylin-eosin staining. The mRNA levels of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the colon tissue were quantified via Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Additionally, the protein and mRNA levels of zonula occludens-1 (ZO-1), Occludin, and Claudin-1 in the colon tissue were assessed by Western blot and Real-time PCR, respectively. Label-free quantitative proteomics was employed to identify the differentially expressed proteins between the colon tissue samples from the blank, model, and HGT groups. Key proteins identified were subsequently validated by Western blot and Real-time PCR. Finally, bioinformatics analysis was conducted on the differentially expressed proteins. ResultsCompared with the blank group, the model group exhibited increased fasting blood glucose, AUC, and GHbA1c levels (P<0.01), damaged colonic mucosal epithelial structure and inflammatory cell infiltration, up-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon and an increase in serum LPS content (P<0.05, P<0.01), and down-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.01). Compared with the model group, the HGT group showed reductions in fasting blood glucose, AUC, and GHbA1c (P<0.01), alleviated damage to the colonic mucosal epithelium, down-regulated mRNA levels of TNF-α, IL-6, and IL-1β in the colon, a reduction in serum LPS content (P<0.05, P<0.01), and up-regulated protein and mRNA levels of ZO-1, Occludin, and Claudin-1 in the colon (P<0.05, P<0.01). Proteomics analysis identified 70 differentially expressed proteins that exhibited a downward trend in the model group relative to the blank group and an upward trend in the HGT group relative to the model group. These findings were corroborated by Western blot and Real-time PCR, which confirmed that the protein and mRNA levels of mucin 2 (Muc2) and transforming growth factor (TGF)-beta receptor 1 (Tgfbr1) in the colon tissue were consistent with the proteomic data. Bioinformatics analysis showed that these 70 differentially expressed proteins identified were significantly enriched in multiple signaling pathways, among which the TGF-β and advanced glycation endproduct (AGE)/receptor for advanced glycation endproduct (RAGE) signaling pathways were closely associated with damage to the intestinal mucosal barrier. This suggests that HGT may ameliorate intestinal mucosal barrier damage by regulating these pathways. ConclusionHGT potentially exerts anti-T2DM effects by influencing AGE/RAGE and TGF-β signaling pathways, thereby contributing to the restoration of the intestinal mucosal barrier.
6.Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities.
Youtao XU ; Qinhong SUN ; Siwei WANG ; Hongyu ZHU ; Guozhang DONG ; Fanchen MENG ; Zhijun XIA ; Jing YOU ; Xiangru KONG ; Jintao WU ; Peng CHEN ; Fangwei YUAN ; Xinyu YU ; Jinfu JI ; Zhitong LI ; Pengcheng ZHU ; Yuxiang SUN ; Tongyan LIU ; Rong YIN ; Lin XU
Chinese Journal of Lung Cancer 2024;26(12):889-900
BACKGROUND:
In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.
METHODS:
A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.
RESULTS:
MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).
CONCLUSIONS
The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans
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Lung Neoplasms/genetics*
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Adenocarcinoma of Lung/genetics*
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China
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Prognosis
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Transcription Factors
7.Chinese Medicine Intervention in Signaling Pathways Related to Diabetic Ulcer: A Review
Xiaotao WEI ; Zhijun HE ; Tao LIU ; Jinfeng WEI ; Jinpeng LI ; Yuan SONG ; Jie CHEN ; Haigang WANG ; Yuanxu HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):212-220
Diabetic ulcer (DU) wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing, and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment, long treatment process, and high morbidity and mortality. Therefore, how to help the rapid healing of DU wounds, reduce the disability rate and mortality rate, protect limb function, and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex, mainly including microcirculation disorder, peripheral neuropathy, inflammation and infection, and excessive apoptosis of cells, involving physiological processes such as wound inflammation, granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Wnt/β-catenin, nuclear factor-κB (NF-κB), Notch, nuclear factor E2-related factor 2 (Nrf2), transforming growth factor-β (TGF-β)/Smad, and other signaling pathways, regulate abnormal glucose metabolism, improve microcirculation, inhibit inflammation and oxidative stress, regulate cell proliferation and excessive apoptosis, and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine (TCM) syndrome differentiation and internal and external treatment. Therefore, this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds, aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.
8.Application of Quality Evaluation of Blind Method in Clinical Trials of Traditional Chinese Medicine
Zeyang SHI ; Yuan SUN ; Wenxin MA ; Yuyi WANG ; Zhijun BU ; Xuehui WANG ; Youyou ZHENG ; Jianping LIU ; Zhaolan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):75-80
The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years, randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine (TCM), but the quality of the implementation of blind methods is uneven, and the evaluation criteria have not yet been formed. In this paper, the data collection methods, calculation principles, advantages, and disadvantages of two quantitative quality evaluation methods of blind methods, namely James Blinding Index (JBI) and Bang Blinding Index (BBI), were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time, a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally, the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.
9.Characteristics and significance of age-related changes in cervical uncinate process-related angle
Dezhou ZHANG ; Chaoqun WANG ; Jun SHI ; Kun LI ; Shaojie ZHANG ; Yuan MA ; Erfei HOU ; Danyang ZHAO ; Yunteng HAO ; Simin WANG ; Xiaohe LI ; Haiyan WANG ; Zhijun LI ; Xing WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5766-5772
BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.
10.Effect of Yiqi Huoxue Tongluo Decoction on miR-126a-5p and VEGF signaling pathway in cervical spondylotic myelopathy model rats
Dan LIU ; Zhanying TANG ; Pan LI ; Weina YUAN ; Fangfang LI ; Qian CHEN ; Zhijun HU
Tianjin Medical Journal 2024;52(3):273-277
Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p(miR-126a-5p)and vascular endothelial growth factor(VEGF)signaling pathway in cervical spondylotic myelopathy model rats.Methods Thirty healthy male SD rats were divided into the sham operation group,the model group and the traditional Chinese medicine(TCM)group by random number table method.Cervical spondylotic myelopathy models were prepared in the model group and the TCM group.The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction,while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks.After intervention,the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests.Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin(HE)staining and observe the number of vascular buds in intervertebral disc.Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining.The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay.Results Compared with the sham operation group,the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group.The cell destruction of intervertebral disc annulus was obvious in rats,and apoptosis was high and cell density decreased.Mechanical stimulation threshold decreased,and mechanical stimulation threshold decreased.The level of miR-126a-5p was decreased,and the expression levels of VEGF mRNA and protein were increased.Compared with the model group,the number of vascular buds in intervertebral disc was increased in the TCM group.The destruction of intervertebral disc annulus cells was alleviated in rats.The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased.The threshold of mechanical stimulation increased,and the retraction time of thermal stimulation was prolonged.The level of miR-126a-5p increased,and the expression levels of VEGF mRNA and protein decreased(P<0.05).Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.

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