1.Mechanism of Mingshi Prescription in Regulating Opn4-dopamine Axis to Inhibit Endoplasmic Reticulum Stress and Delay Myopia Progression
Baohua LI ; Zefeng KANG ; Lulu WANG ; Xin YAN ; Jianquan WANG ; Xinyue HOU ; Bobiao NING ; Shanshan YE ; Mengyu LIU ; Yipeng SHI ; Danyu LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):58-67
ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine (Opn4-DA) axis in myopic mice to inhibit endoplasmic reticulum (ER) stress in the retina and sclera, thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group, a form-deprived myopia group (FDM group), an intrinsically photosensitive retinal ganglion cells ablation group (ipRGCs group), a Mingshi Prescription group (MSF group, 5.2 g·kg-1), and an ipRGCs + MSF group (5.2 g·kg-1). Except for the normal group, all other groups underwent FDM modeling. Additionally, the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling, the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice, eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina, choroid, and sclera were observed using periodic acid-Schiff (PAS) staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor (DRD1), C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) in the retina, and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4, CHOP, and GRP78 in the retina, and CHOP and GRP78 in the sclera. Immunofluorescence staining (IF) was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group, the FDM group showed a significant myopic shift in refraction (P<0.05) and a significant increase in axial length (P<0.05). The retinal layers were thinner, the number of ganglion cells was reduced, and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased (P<0.05), while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased (P<0.05). Compared with the FDM group, the ipRGCs group exhibited further increases in myopic refraction and axial length (P<0.05), more pronounced thinning and looseness in the retinal, choroidal, and scleral layers, lower expression of Opn4 and DRD1 protein and mRNA in the retina (P<0.05), and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera (P<0.05). Compared with the FDM group, the MSF group showed significantly reduced refractive error and axial length (P<0.05), with improved cellular number, arrangement, and thickness in ocular tissues, increased Opn4 and DRD1 protein and mRNA expression in the retina (P<0.05), and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera (P<0.05). Similarly, the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group (P<0.05). ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice, thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes, softens the fascia, and restores ocular rhythm.
2.Neuroprotective effect of Dendrobium nobile Lindl extract on Caenorhabditis elegans model of Parkinson's disease
Xinyue FAN ; Wenlu HE ; Li DONG ; Zhiying HOU ; Hanwen ZHENG ; Qiong WANG
Chinese Journal of Comparative Medicine 2025;35(4):31-42
Objective To investigate the neuroprotective effect of Dendrobium nobile Lindl(DNL)extract in a Caenorhabditis elegans(C.elegans)model of Parkinson's disease(PD).Methods C.elegans NL5901 and 6-hydroxydopamine(6-OHDA)induced N2,BZ555,PD4521,and CB7272 C.elegans strains were treated with DNL 7.5,15,and 30 mg/L.The survival rate,basal slowing response rate,α-synuclein(α-syn)aggregation,dopaminergic neurons(DNs),mitochondrial distribution density of body wall muscle cells,and protein levels in the membrane were observed.In addition,reactive oxygen species(ROS),superoxide dismutase(SOD)and glutathione(GSH)in 6-OHDA induced N2 was detected to explore the effect of DNL on the antioxidative stress ability of PD C.elegans models.Results Compared with that in the model group,the DN fluorescence intensity was significantly increased in nematodes treated with DNL and levodopa(L-DOPA)(P<0.05,P<0.0001),α-syn aggregation was significantly decreased(P<0.05,P<0.001,P<0.0001),the basal slowing rate(P<0.05,P<0.01,P<0.001),mitochondrial density(P<0.05,P<0.01,P<0.001),mitochondrial intima protein content(P<0.05,P<0.001,P<0.0001),SOD content(P<0.05),and GSH content were all increased.The ROS content was reduced in nematodes(P<0.01).The lifespans of N2 wild-type and PD C.elegans models were prolonged after DNL treatment(P<0.05,P<0.01,P<0.001).Conclusions DNL can effectively improve motor paralysis in a C.elegans PD model,improve DN degradation,inhibit α-syn aggregation and neuronal damage,increase the antioxidative stress ability,and slow the aging process in C.elegans.
3.Damage Characteristics of Peri-implant Bones with Varying Densities under Impact and Occlusal Forces
Xinyang MA ; Xiaoou DIAO ; Bing HOU ; Xinyue ZHANG ; Hui ZENG
Journal of Medical Biomechanics 2025;40(4):872-877
Objective To investigate the damage characteristics of peri-implant bones with varying densities under impact and occlusal forces using numerical simulation.Methods A finite element model of the microstructure of an implant and bones with different densities was established.Impact and occlusal forces were applied sequentially to the implant.A user material subroutine was created for failure judgment using stress-based failure criteria,enabling the analysis of bone damage caused by impact and occlusal forces.Results No cortical bone damage was observed in bones of varying densities under impact force.Damage primarily occurred in the trabecular bone at the base of the implant,with the extent of damage worsening as bone density decreased.Additionally,the number of failed bone elements generated by the damage increased with reduced bone density.Bone tissues with pre-existing impact damage sustained secondary damage when subjected to occlusal force:the bonding interface between the implant and cortical bone was damaged,leading to implant displacement and fracture of peri-implant trabecular bone.The damage caused by occlusal force also worsened as bone density decreased.Conclusions The degree of damage from impact and occlusal forces is correlated with bone density,with damage worsening as bone density decreases.This underscores the protective role of cortical bone.The application of occlusal force exacerbates bone tissue damage,leading to implant displacement when the cortical bone is damaged.In clinical practice,patients with a history of impact damage should undergo thorough examination and evaluation.The occlusal force borne by damaged bones should be reduced;if necessary,the implant should be removed and reinserted after re-establishment of osseointegration.
4.Neuroprotective effect of Dendrobium nobile Lindl extract on Caenorhabditis elegans model of Parkinson's disease
Xinyue FAN ; Wenlu HE ; Li DONG ; Zhiying HOU ; Hanwen ZHENG ; Qiong WANG
Chinese Journal of Comparative Medicine 2025;35(4):31-42
Objective To investigate the neuroprotective effect of Dendrobium nobile Lindl(DNL)extract in a Caenorhabditis elegans(C.elegans)model of Parkinson's disease(PD).Methods C.elegans NL5901 and 6-hydroxydopamine(6-OHDA)induced N2,BZ555,PD4521,and CB7272 C.elegans strains were treated with DNL 7.5,15,and 30 mg/L.The survival rate,basal slowing response rate,α-synuclein(α-syn)aggregation,dopaminergic neurons(DNs),mitochondrial distribution density of body wall muscle cells,and protein levels in the membrane were observed.In addition,reactive oxygen species(ROS),superoxide dismutase(SOD)and glutathione(GSH)in 6-OHDA induced N2 was detected to explore the effect of DNL on the antioxidative stress ability of PD C.elegans models.Results Compared with that in the model group,the DN fluorescence intensity was significantly increased in nematodes treated with DNL and levodopa(L-DOPA)(P<0.05,P<0.0001),α-syn aggregation was significantly decreased(P<0.05,P<0.001,P<0.0001),the basal slowing rate(P<0.05,P<0.01,P<0.001),mitochondrial density(P<0.05,P<0.01,P<0.001),mitochondrial intima protein content(P<0.05,P<0.001,P<0.0001),SOD content(P<0.05),and GSH content were all increased.The ROS content was reduced in nematodes(P<0.01).The lifespans of N2 wild-type and PD C.elegans models were prolonged after DNL treatment(P<0.05,P<0.01,P<0.001).Conclusions DNL can effectively improve motor paralysis in a C.elegans PD model,improve DN degradation,inhibit α-syn aggregation and neuronal damage,increase the antioxidative stress ability,and slow the aging process in C.elegans.
5.Damage Characteristics of Peri-implant Bones with Varying Densities under Impact and Occlusal Forces
Xinyang MA ; Xiaoou DIAO ; Bing HOU ; Xinyue ZHANG ; Hui ZENG
Journal of Medical Biomechanics 2025;40(4):872-877
Objective To investigate the damage characteristics of peri-implant bones with varying densities under impact and occlusal forces using numerical simulation.Methods A finite element model of the microstructure of an implant and bones with different densities was established.Impact and occlusal forces were applied sequentially to the implant.A user material subroutine was created for failure judgment using stress-based failure criteria,enabling the analysis of bone damage caused by impact and occlusal forces.Results No cortical bone damage was observed in bones of varying densities under impact force.Damage primarily occurred in the trabecular bone at the base of the implant,with the extent of damage worsening as bone density decreased.Additionally,the number of failed bone elements generated by the damage increased with reduced bone density.Bone tissues with pre-existing impact damage sustained secondary damage when subjected to occlusal force:the bonding interface between the implant and cortical bone was damaged,leading to implant displacement and fracture of peri-implant trabecular bone.The damage caused by occlusal force also worsened as bone density decreased.Conclusions The degree of damage from impact and occlusal forces is correlated with bone density,with damage worsening as bone density decreases.This underscores the protective role of cortical bone.The application of occlusal force exacerbates bone tissue damage,leading to implant displacement when the cortical bone is damaged.In clinical practice,patients with a history of impact damage should undergo thorough examination and evaluation.The occlusal force borne by damaged bones should be reduced;if necessary,the implant should be removed and reinserted after re-establishment of osseointegration.
6.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.
7.Mingshi Formula (明视方) for Low Myopia in Children with Heart Yang Insufficiency Syndrome: A Multicentre, Double-Blind, Randomised Placebo-Controlled Study
Jianquan WANG ; Xinyue HOU ; Zefeng KANG ; Yingxin YANG ; Xinquan LIU ; Zhihua SHEN ; Xiaoyi YU ; Jing YAO ; Fengming LIANG ; Fengmei ZHANG ; Jingsheng YU ; Ningli WANG ; Man SONG ; Hongrui SUN ; Xin YAN
Journal of Traditional Chinese Medicine 2024;65(6):587-593
ObjectiveTo observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules (明视方颗粒) for low myopia in children with heart yang insufficiency. MethodsA multicentre, prospective, double-blind randomised controlled study was conducted, in which 290 children with low myopia from 8 centres were randomly divided into 145 cases in the treatment group and 145 cases in the control group, and the treatment group was given education, dispensing glasses, and Chinese herbal medicine Mingshi Granules, while the control group was given education, dispensing glasses, and granules placebo. Both Mingshi Granules and placebo granules were taken orally, 1 bag each time, twice daily, 4 weeks of oral intake and 2 weeks of rest as 1 course of treatment, a total of 4 courses of treatment (24 weeks). Equivalent spherical lenses, best naked-eye distance visual acuity, ocular axis, corneal curvature K1, adjustment amplitude, traditional Chinese medicine (TCM) symptom scores, calculate the amount of progression of equivalent spherical lenses, were observed at the 12th and the 24th week of treatment, at the 36th week and 48th week of follow-up, resectively, the control rate of myopia progression was evaluated at the 24th week, and safety indexes were observed before treatment. ResultsThe amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up (P<0.05). The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher (57.60%, 72/125) than that in the control group (44.63%, 54/121) (P<0.05). The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group (P<0.05). Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment (P<0.05), and were higher in the treatment group than in the control group at the 48-week follow-up (P<0.05). The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment (P<0.05). The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up (P<0.05). Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment (P<0.05). The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treatment (P<0.05). The scores of white/dark complexion, white coating thin pulse, fatigue and total TCM symptom scores of children in both groups at the 12th, 24th, 36th and 48th weeks of follow-up were significantly lower than those before treatment (P<0.05); the scores of blurred vision at the 24th and 36th weeks of follow-up were significantly lower than those before treatment (P<0.05); and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment (P<0.05). In the treatment group, the score of fatigue was higher than that of the control group at the 36-week follow-up, and the score of blurred vision was lower than that of the control group at the 48-week follow-up (P<0.05). No adverse reactions or obvious abnormalities of the safety indexes were observed of the two groups during the treatment. ConclusionChinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia, improving the best naked eye distance visual acuity, slowing down the growth of the eye axis, improving some of the TCM symptoms, with good safety.
8.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.
9.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.
10.Research trends and hotspots of anti-Müllerian hormone from 2006 to 2020
Chao DU ; Xinyue FAN ; Kaibo HOU ; Xiaochuan GUAN ; Bolun WANG ; Yan GAO ; Yuexin YU
Chinese Journal of Reproduction and Contraception 2023;43(5):541-547
Objective:To analyze the research trends and hotspots of anti-Müllerian hormones (AMH) from 2006 to 2020, and to provide reference for future research in related fields.Methods:Based on the PubMed database, the literatures related to AMH collected from January 1st, 2006 to December 31st, 2020 were retrieved, and the bibliometric method was used to analyze the relationship between each stage and AMH with every 5 years as the time node. The publication trends, high-frequency main MeSH/subheadings co-occurrence and research hotspots related to AMH were discussed and forecasted.Results:A total of 4 276 related literatures were retrieved in this paper, and the total number of published papers showed an increasing trend. Relevant research hotspots were gradually increasing. The core research from 2005 to 2010 was the biomarker effect of AMH; from 2011 to 2015 and 2016 to 2020, the core research hotspots were all AMH and polycystic ovary syndrome.Conclusion:While the research hotspots related to AMH have been continuously expanded and enriched, there are also certain changes and alternations, and some emerging hotspots still have the value and significance of further research. AMH type Ⅱ receptor and fertility preservation may become an emerging hotspot in this field in the future.

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