1.Treatment of Diabetic Kidney Disease with Traditional Chinese Medicine Based on Epithelial-to-mesenchymal Transition-related Pathways: A Review
Jintao SHI ; Zhiyi ZHANG ; Yushan GAO ; Baicun GUO ; Yifei HU ; Jiarui HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):288-298
Diabetic kidney disease (DKD) stands as one of the most prevalent microvascular complications of diabetes,noted for its concealed onset and tendency to evolve into end-stage renal disease,profoundly impacting patients' life expectancy and quality of life. Epithelial-to-mesenchymal transition (EMT) is a central pathological process in the initiation and progression of DKD,facilitating disease advancement and renal fibrosis,thus representing a crucial focus of research into the pathological mechanisms of DKD. EMT is driven by the abnormal activation of signaling pathways,including transforming growth factor-β (TGF-β)/Smad,secreted glycoprotein/β-catenin,Notch,tumor necrosis factor-α (TNF-α)/nuclear factor-κB (NF-κB),and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR),leading to renal cellular injury and subsequently accelerating renal fibrosis and the progression of DKD. Traditional Chinese medicine (TCM),characterized by its multi-target and multi-pathway therapeutic approach,demonstrates unique advantages in addressing DKD and EMT. Recent research has shown that active ingredients in TCM,including glycosides,flavonoids,and polyphenols,as well as TCM formulas,can precisely target these relevant signaling pathways,effectively inhibiting cellular injury in DKD and intervening in the EMT process. These findings not only underscore the potential of TCM monomers and formulas in treating DKD and EMT but also pave new directions for research in this field within TCM. This paper systematically reviewed the signaling pathways associated with EMT and provided an in-depth analysis of the research achievements and underlying mechanisms of TCM monomers and formulas in treating DKD and intervening in EMT,aiming to offer new insights and directions for TCM in the treatment of DKD and research on EMT,thereby further promoting the modernization and development of TCM.
2.Study on Pre-Clinical In-Vitro Test Methods of Unicondylar Knee Prosthesis.
Shu YANG ; Dan HAN ; Wen CUI ; Zhenxian CHEN ; Jinju DING ; Jintao GAO ; Bin LIU
Chinese Journal of Medical Instrumentation 2025;49(1):111-118
Compared with total knee arthroplasty, unicondylar knee replacement has the advantage of preserving the knee tissue structure and motor function to the greatest extent. Pre-clinical in-vitro test is an important tool to evaluate the safety and effectiveness of unicondylar knee prostheses, and it is also a key focus of the product registration process. Through collection, comparison, and analysis of current regulations, technical standards, guidelines, and related research literature, this paper expounds on the relevant research methods for the pre-clinical in-vitrotesting of unicondylar knee prostheses. At the same time, in conjunction with current evaluation requirements and experience, the study discusses the focus of pre-clinical performance research for unicondylar knee prostheses during the registration process to clarify the performance evaluation requirements of this product category. This aims to provide a reference for the pre-clinical performance research of unicondylar knee prostheses and to standardize industry testing standards.
Knee Prosthesis
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Arthroplasty, Replacement, Knee
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Humans
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Prosthesis Design
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Materials Testing
4.Enhanced BBB penetration and microglia-targeting nanomodulator for the two-pronged modulation of chronically activated microglia-mediated neuroinflammation in Alzheimer's disease.
Ya WEI ; Xue XIA ; Xiaorong WANG ; Wenqin YANG ; Siqin HE ; Lulu WANG ; Yongke CHEN ; Yang ZHOU ; Feng CHEN ; Hanmei LI ; Fu PENG ; Guobo LI ; Zheng XU ; Jintao FU ; Huile GAO
Acta Pharmaceutica Sinica B 2025;15(2):1098-1111
Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.
5.Study of Typical Functional Failure and Mechanical Properties of Non-absorbable Suture Anchor.
Jintao GAO ; Zhen ZHEN ; Dan HAN ; Bin LIU
Chinese Journal of Medical Instrumentation 2023;47(3):247-251
OBJECTIVE:
To study the mechanical properties related to the typical functional failure modes of non-absorbable suture anchor in clinical use, and to support product design, development and verification.
METHODS:
By retrieving the database of relevant adverse events, the typical functional failure modes of non-absorbable suture anchor were summarized, and the influencing factors of functional failure were further analyzed by studying the mechanical properties related to functional failure. The publicly available test data was retrieved for verification and provided reference for the researchers.
RESULTS:
The typical functional failure modes of non-absorbable suture anchor include anchor failure, suture failure, fix loosening, inserter failure, which are related to the mechanical properties of products, such as screw-in torque and break torque of screw-in anchors, insertion force of knock-in anchors, suture strength, pull-out force before and after system fatigue test and elongation of sutures after fatigue test.
CONCLUSIONS
Enterprises should pay attention to improving the mechanical performance level of products through material, structural design and the suture weaving process to ensure the safety and effectiveness of products.
Suture Anchors
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Suture Techniques
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Sutures
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Absorbable Implants
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Biomechanical Phenomena
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Materials Testing
6.Concerns of Technical Evaluation on Registration of All-inside Meniscus Suture System.
Jintao GAO ; Ruhan A ; Jing WU ; Bin LIU
Chinese Journal of Medical Instrumentation 2023;47(4):437-441
OBJECTIVE:
To summarize the product registration declaration ideas and registration technical review of the all-inside meniscal suture system, and to systematically think about of the technical review concerns of the all-inside meniscal suture system products to provide technical guidance for improving the quality of registration and application and regulatory efficiency.
METHODS:
Consult the public information of such products at home and abroad, and summarize the experience of registration review of such products.
RESULTS:
The technical review of the all-inside meniscus suture system registration mainly focuses on product basic information, pre-clinical research, clinical evaluation and product technical requirements.
CONCLUSIONS
The difficulty of product registration and declaration of the all-inside meniscus suture system lies in the provision of pre-clinical research data of the product, and the applicant needs to strengthen the basic research ability, formulate scientific technical indicators and test methods to ensure the safety and effectiveness of the product, and also provide sufficient supporting data for the registration declaration.
Humans
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Menisci, Tibial/surgery*
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Suture Techniques
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Tibial Meniscus Injuries/surgery*
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Sutures
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Arthroscopy/methods*
7.Effects of hnRNP E1 on expression of early genes E2, E6 of HPV16 and biological function in cervical cancer cells
Li SONG ; Ling DING ; Meijuan FENG ; Xiaoxue LI ; Wen GAO ; Zhuo QI ; Hong LIU ; Ming WANG ; Jintao WANG
Chinese Journal of Epidemiology 2021;42(2):321-326
Objective:To explore the effects of hnRNP E1 on the expression of early genes E2, E6 of HPV16 and the biological function in cervical cancer SiHa cell lines.Methods:The cell experiments in vitro were carried out in cervical cancer cell lines SiHa. The expression levels of E2, E6 mRNA and protein of HPV16 were detected by Real-time PCR and Western blot, respectively, before and after up-regulating hnRNP E1. Meanwhile, the cell proliferation, cycle and apoptosis were evaluated by CCK-8 and flow cytometry. Data analyses were performed using SPSS 22.0 and Graphpad Prism 7.0 software. Results:Compared with the blank and the blank plasmid group, the cells activity and proliferation decreased at 24, 48 and 72 h after up-regulating hnRNP E1 ( P<0.05), while the percentage of cells in G0/G1 phase increased and the percentage in S and G2/M phase and proliferation index decreased ( P<0.05). Moreover, the late apoptotic rate and the total apoptotic rate increased ( P<0.05). The expression levels of E6 mRNA and protein of HPV16 in hnRNP E1 up-regulated group were significantly lower than that in both blank group and blank plasmid group, the differences were significant ( P<0.05), showing the tendency of cells proliferation index decrease and total apoptotic rate increase with decreased HPV16 E6 expression. There were no significant differences in the expression of E2 mRNA of HPV16 among the three groups ( P=0.427), and no E2 protein of HPV16 was detected. Conclusions:hnRNP E1 could inhibit the transcription and translation of E6 oncogene of HPV16 and further inhibit the proliferation and promote apoptosis of cervical cancer cells, suggesting that hnRNP E1 might be a potential target marker to prevent cervical lesions. But no association between hnRNP E1 and HPV16 E2 was found in SiHa cells.
8. The role of human papillomavirus 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein E2 in cervical carcinogenesis and their interaction effect
Wen GAO ; Ling DING ; Zhichao SONG ; Meijuan FENG ; Chunliang LIU ; Xiaoxue LI ; Li SONG ; Yuanjing LYU ; Jintao WANG
Chinese Journal of Preventive Medicine 2020;54(1):92-98
Objective:
To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer.
Methods:
Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model.
Results:
The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about
9.Relations of human papillomavirus infection, vaginal micro-environmental disorder with cervical lesion
Xiaoxue LI ; Ling DING ; Li SONG ; Wen GAO ; Li LI ; Yuanjing LYU ; Ming WANG ; Min HAO ; Zhilian WANG ; Jintao WANG
Chinese Journal of Epidemiology 2020;41(12):2135-2140
Objective:To study the relations of human papillomavirus (HPV) infection, vaginal micro-environmental disorder with cervical lesion.Methods:A total of 1 019 women including 623 with normal cervical (NC), 303 with low-grade cervical lesion (CIN Ⅰ) and 93 with high-grade cervical lesion (CIN Ⅱ/Ⅲ) were enrolled in this study from the communities in Shanxi province, China. Case-control method was adopted, with NC as the control group and CIN as the case group. Related information was collected including demographic characteristics and relevant factors related to cervical lesions. HPV genotypes were detected by flow-through hybridization technology. Vaginal pH was detected by the pH test paper. Vaginal H 2O 2 was detected by the combined detection kit of aerobic vaginitis and bacterial vaginosis. Vaginal cleanliness was detected by smear method. Results:Data from the unconditional logistic regression analysis showed that HPV infection (CINⅠ: a OR=1.39, 95 %CI: 1.01-1.90; CINⅡ/Ⅲ: a OR=11.74, 95 %CI: 6.96-19.80), H 2O 2 (CINⅠ: a OR=2.09, 95 %CI: 1.47-2.98; CINⅡ/Ⅲ: a OR=4.12, 95 %CI: 2.01-8.43), cleanliness (CIN Ⅱ/Ⅲ: a OR=2.62, 95 %CI: 1.65-4.14), and composite indicators (CINⅠ: a OR=1.67, 95 %CI: 1.24-2.25; CINⅡ/Ⅲ: a OR=4.24, 95 %CI: 2.30-7.81) all had increased the risk of cervical lesion and the trend on the severity ( P<0.001) of cervical lesions. Additionally, we observed a synergic effect between HPV infection and vaginal micro-environmental composite indicator in CINⅡ/Ⅲ. With or without HPV infection, the ORs value of CINⅠ caused by vaginal micro-environment disorder remained close. Conclusions:Results from our study revealed that vaginal micro-environmental composite indicator could increase the risk for cervical lesion, in particular with the high-grade ones which all posed stronger risks when combined with HPV infection. However, the role of vaginal micro-environment disorder in the occurrence of CIN Ⅰ should not be ignored.
10.Expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis
Jintao LIU ; Ling GAO ; Huiui ZHOU
Practical Oncology Journal 2019;33(4):334-339
Objective The aim of this study was to investigate the expression of MAGEA4 and EB1 proteins in lung cancer tissues and their correlation with clinicopathological features and prognosis. Methods A total of 136 patients with lung cancer in our hospital were enrolled. The expression levels of MAGEA4 and EB1 at levels of mRNA and protein were measured by real-time fluo-rescence reverse transcription and immunohistochemistry. The correlation between MAGEA4 and EB1 expression and clinical patholog-ical features,and prognosis were analyzed by χ2 test and Cox regression analysis. Results The expression of MAGEA4 and EB1 mR-NA in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 in lung canc-er tissues were higher than those in adjacent tissues(P<0. 05). The expression of MAGEA4 and EB1 proteins in lung cancer tissues was higher than those in adjacent tissues(P<0. 05). The positive rates of MAGEA4 and EB1 proteins were not significantly correlated with age(P>0. 05),but they were related to the maximum diameter,pathological grade,TNM stage,infiltration depth,lymphatic vas-cular infiltration,lymph node metastasis and recurrence(P<0. 05). The 3-year survival rate and total survival time of MAGEA4 and EB1 negative group were significantly higher than those of MAGEA4 and EB1 positive group(P<0. 05). Lymphatic vascular infiltra-tion,lymph node metastasis,MAGEA4 positive and EB positive were independent risk factors for prognosis of patients with lung cancer (P<0. 05). Conclusion The positive expression rates of MAGEA4 and EB1 proteins in lung cancer tissues are increased,and their high expression may be related to the occurrence and development of lung cancer. Lung cancer patients with negative expression of MAGEA4 and EB1 proteins can obtain better prognosis.

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