1.Causal relationship between sex steroid hormones and myopia:a Mendelian randomization study
Baohua LI ; Zefeng KANG ; Mingming ZHANG ; Xinyue HOU ; Jianquan WANG ; Danyu LI ; Mengyu LIU ; Yipeng SHI
Recent Advances in Ophthalmology 2024;44(12):961-966
Objective To analyze the causal relationship between serum sex steroid hormone levels and myopia with the Mendelian randomization(MR)methods.Methods Sex hormone genetic tools classified by sex were publicly availa-ble summarized statistical data from the Genome-wide association study(GWAS)of the UK Biobank Consortium on sex hormone-binding globulin(SHBG),total testosterone(TT),bioavailable testosterone(BT),and estradiol(E2).The GWAS summarized statistical data for myopia were obtained from publicly available data published by the FinnGen Consorti-um R10.All data were downloaded from April 18 to April 31,2024 from the corresponding databases and analyzed.All re-sults from the MR study were mainly analyzed by inverse-variance weighting(IVW)method.Results The study showed that a higher serum SHBG level in European increased the risk of myopia development in women(IVW,OR=1.152,95%CI:1.014-1.308,P=0.029);low serum TT level(IVW,OR=0.821,95%CI:0.697-0.967,P=0.018)and serum BT lev-el(IVW,OR=0.820,95%CI:0.691-0.972,P=0.022)increased the risk of myopia development in women.There was no causal relationship between serum SHBG,TT,and BT levels and myopia in men.There was no causal effect between E2 level and myopia in women and men.The stability of our findings was supported by sensitivity analysis.Conclusion In-creased serum SHBG level and decreased serum TT and BT levels are associated with an increased risk of myopia in women,whereas no such association is found in men.There is no causal relationship between E2 and myopia.
2.Evaluation of A Liver Yin Deficiency Mouse Model Based on Untargeted Metabolomics
Xuening HUANG ; Xia ZHAO ; Mengyu HOU ; Zhiyu GUO ; Yaohui YE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):118-125
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS), to evaluate the establishment of a mouse model of liver Yin deficiency by thyroid tablet suspension combined with 10% carbon tetrachloride(CCl4) from the perspective of non-targeted metabolomics, in order to lay the foundation for the establishment of a traditional Chinese medicine(TCM) syndrome model. MethodA total of 24 mice were randomly divided into blank group and model group. The model group was given thyroid tablet suspension(0.003 2 g·kg-1) by gavage for 14 consecutive days, and 10% CCl4(5 mL·kg-1) was intraperitoneally injected once a week to establish a liver Yin deficiency model, while the blank group was injected with an equal amount of olive oil intraperitoneally and gavaged with an equal amount of distilled water, and was fed with normal feed. After the modeling was completed, 6 mice in each group were randomly selected, the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), interleukin(IL)-6, IL-10, tumor necrosis factor-α(TNF-α)were measured in the mice serum, and malondialdehyde(MDA), superoxide dismutase(SOD), total protein(TP), hydroxyproline(HYP) and other indicators were measured in the mice liver. Liver tissue sections were taken for hematoxylin-eosin(HE) staining and observing pathological changes. The remaining 6 mice in each group were subjected to UPLC-Q-TOF-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen differential metabolites in the liver Yin deficiency mouse model, Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used to analyze the corresponding metabolic pathways of differential metabolites. ResultCompared with the blank group, mice in the model group showed liver Yin deficiency manifestations such as reduced body weight, fatigue and sleepiness, disheveled and lusterless hair, irritability. The levels of ALT, cAMP/cGMP, IL-6, AST, MDA, cAMP, TNF-α significantly increased(P<0.05, P<0.01), while the levels of SOD, IL-10 and cGMP significantly decreased(P<0.05, P<0.01), and the changes of HYP and TP were not statistically significant. Hepatic steatosis and distortion of the radial arrangement of the liver plate cells were seen in the section images of the model group, endogenous substances were clearly separated, and 252 differential metabolites were identified in the serum samples, which were mainly involved in the metabolic pathways of purine metabolism, steroid hormone biosynthesis and pyrimidine metabolism. A total of 229 differential metabolites were identified in the liver samples, mainly involving nucleotide metabolism, purine metabolism, steroid hormone biosynthesis, pyrimidine metabolism, antifolate resistance, insulin resistance, primary bile acid biosynthesis, prostate cancer, sulfur relay system, arachidonic acid metabolism and other metabolic pathways. ConclusionThe successful establishment of liver Yin deficiency model in mice by CCl4 combined with thyroid hormone is evaluated through the investigation of serum and liver metabolomics, combined with biochemical indicators, which provides a biological basis and experimental foundation for the Yin deficiency syndrome model of TCM.
3.Study on the Efficacy of Cervi Colla in Yiqi Buxue Based on the Zebrafish Model
Yutong LIU ; Yong HUANG ; Hongyun MAO ; Tong ZHANG ; Jie CUI ; Mengyu LI ; Rong HOU ; Yunfeng ZHENG ; Yongqing HUA
Herald of Medicine 2023;42(12):1765-1771
Objective To quickly observe the tonic effects of Cervi Colla on enriching blood,strengthening bones and anti-aging in zebrafish model.Methods Glyphosate(Gly)was used to construct the erythrocyte injury model in adult zebrafish,and methotrexate(MTX)was used to construct the hematopoietic function injury model of juvenile zebrafish.Prednisolone(Pred)was used to establish the inhibition model of bone formation in zebrafish larvae.The ocular cell apoptosis model of zebrafish larvae was established by dibutyl phthalate(DBP).Results Cervi Colla could improve the Gly-induced abnormal erythrocyte nucleus in adult zebrafish and promote the expression of hematopoietic factors SCL and GATA1.Cervi Colla improved Pred-induced inhibition of bone formation in juvenile zebrafish,and promoted the expression of osteoblast-related gene ALP and Runx2a.The number of ocular cell apoptosis induced by DBP was decreased,and the expression of anti-apoptotic factor Bcl-2 was promoted.Conclusion Cervi Colla has significant effects on protecting erythrocyte,protecting hematopoiesis,protecting bone formation and anti-apoptosis.These effects may be related to replenish blood,anti-osteoporosis,and anti-aging.This study provides a scientific basis for the clinical application of Cervi Colla,and lays a foundation for further development and application.
4.Discussion on the"brain-eye"mechanism of myopia from the"theory of imbalance of the essence and tendon"
Danyu LI ; Zefeng KANG ; Xin YAN ; Hongrui SUN ; Baohua LI ; Mengyu LIU ; Xinyue HOU ; Hua PENG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):971-976
Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.
5.Spectrum-effect Relationship of Bupleuri Radix Processed with Trionyx sinensis Blood for Yin Deficiency Based on Saponins
Mengyu HOU ; Xia ZHAO ; Zhiyu GUO ; Ting LIU ; Yuexing MA ; Yaohui YE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):147-155
ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood, and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM (version 2012). A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine (T3), thyroxine (T4), cyclic adenosine phosphate (cAMP), and cyclic guanosine phosphate (cGMP). The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database (TCMSP), The Encyclopedia of Traditional Chinese Medicine (ETCM), and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). Furthermore, the Online Mendelian Inheritance in Man (OMIM), GeneCards, TTD, DisGeNET, and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group, the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP, cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B1 > saikosaponin B2 > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A, D, B1, and B2 had higher VIP values. Network pharmacology predicted a total of 30 common targets, which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9, kinase insert domain receptor (KDR), and mammalian target of rapamycin (mTOR) and higher mRNA level of mouse double minute 2 homolog (MDM2) than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome, which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.
6.Regulatory role of PI3K/AKT pathway in diabetic retinopathy
Baohua LI ; Zefeng KANG ; Xinyue HOU ; Jianquan WANG ; Man SONG ; Danyu LI ; Mengyu LIU ; Xin YAN
International Eye Science 2024;24(9):1426-1431
Diabetic retinopathy(DR)is one of the major complications of diabetes mellitus, characterized by neurodegeneration and microangiopathy. Currently, the treatment of DR is mainly focused on the management of late complications and has not achieved the desired clinical outcome. Evidence suggests that the PI3K/AKT pathway, as one of the important intracellular signaling pathways during the cell cycle, is involved in the whole process of DR pathogenesis. This article focuses on the structural composition, activation and blocking pathways, conduction pathways, regulatory mechanisms and biological functions of the PI3K/AKT signaling pathway to review its role in DR and to explore the potential of targeting the PI3K/AKT pathway for the treatment of DR.