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.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.
3.Development and application of regulatory T cells in corneal transplant rejection
Xin DU ; Ruijuan GUAN ; Zefeng KANG ; Ling LI ; Xin YAN ; Xiaoying ZHANG
International Eye Science 2024;24(8):1246-1249
Corneal transplantation is an effective treatment for corneal blindness, and it is the only hope for patients with corneal blindness. Cornea has no blood vessels and no lymphatic vessels, which is called immune privilege organ, so the success rate of corneal transplantation is significantly higher than that of other organ transplantation, but the rejection reaction after corneal transplantation is still the main reason for the failure of corneal transplantation. The directional movement of immune cells to lymphoid tissue and inflammatory sites is the mainly immune response after organ transplantation. And the regulatory T cells(Treg)play a key role in immune regulation, which can induce immune tolerance by regulating and inhibiting the activation of effector T cells and reduce the rejection reaction after corneal transplantation. In addition, this review also discussed the effectiveness of applying cordyceps sinensis extract FTY720 to enhance the function of Treg. Based on this, we briefly reviewed the sources, mechanism of action and treatment of Treg after corneal transplantation, so as to provide some reference for the subsequent clinical application transformation and basic research.
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.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.
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.Advances in research on relationship between indoor artificial light at night and human health
Fengrui ZHU ; Zefeng KANG ; Furong DENG
Journal of Environmental and Occupational Medicine 2024;41(2):214-218
With the acceleration of global urbanization, the intensity and coverage of artificial light at night (ALAN) are increasing, and its service duration is obviously prolonged. ALAN exposure is not only related to the occurrence and development of cardiovascular, metabolic, sleep, myopia, and mental diseases, but also may induce cancer. Previous studies have focused on the health effects of outdoor ALAN, but people spend more than 80% of their lives indoors, hence it is of great significance to understand the relationship between indoor ALAN and population health to create a healthy indoor environment and protect the health of the population.
8.Pressure-induced differentiation of rabbit retinal stem cells into retinal ganglion cells
Min DAI ; Zefeng KANG ; Zhulin HU ; Yan LI
Chinese Journal of Experimental Ophthalmology 2022;40(12):1134-1140
Objective:To investigate the effect of pressure on the differentiation of rabbit retinal stem cells (RSCs) co-cultured with retinal ganglion cells (RGCs).Methods:SPF grade New Zealand rabbits on the day 22 of gestation were selected, and embryos were removed to obtain retinal ciliary margin pigment epithelial tissue and culture primary RSCs.Six SPF grade newborn New Zealand rabbits were selected, and retinal neuroepithelial layer tissues were isolated to culture primary RGCs.Rabbit RSCs cultured in vitro were identified by immunofluorescence staining of nestin antibody, bromodeoxyuridine (BrdU) cell proliferation assay kit, RSCs spontaneously differentiated cells immunofluorescence detection and flow cytometry.RGCs were identified through immunofluorescence staining of Brn3b antibody and Thy1.1 antibody.A co-culture system of RGCs and RSCs cultured in the upper and lower layers of a transwelll plate respectively was constructed.The mRNA and protein expression levels of nestin and Thy1.1 in RSCs and differentiated cells under pressures of 0, 20, 40, 60, 80 mmHg (1 mmHg=0.133 kPa) were detected by real-time fluorescence quantitative PCR and Western blot.The feeding and use of laboratory animals were in accordance with the Regulations on the Administration of Laboratory Animals promulgated by the State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Yunnan University Affiliated Hospital (No.KPRC-IACUC17008). Results:RSCs cultured in vitro were nestin-positive.The percentage of BrdU-positive isolated RSCs was (92.26±3.28)%.Some cells differentiated from RSCs were Brn3b-positive, accounting for (13.00±3.06)%, and some were GS-positive, accounting for (31.60±3.67)%.RGCs cultured in vitro were Brn3b- and Thy1.1-positive.There were statistically significant differences in the relative mRNA and protein expressions of nestin and Thy1.1 between RSCs and differentiated cells under different pressures (mRNA: F=127.600, 137.400; both at P<0.01; protein: F=82.480, 158.700; both at P<0.001). The relative mRNA and protein expressions of nestin were significantly reduced in RSCs, and relative mRNA and protein expressions of Thy1.1 were significantly increased in differentiated cells at 20, 40, 60 and 80 mmHg in comparison with 0 mmHg (all at P<0.05). When the pressure was 40 mmHg, the relative mRNA and protein expressions of nestin were lowest in RSCs, and the relative mRNA and protein expressions of Thy1.1 in differentiated cells were highest. Conclusions:Within a certain range, pressure can promote the differentiation of RSCs co-cultured with RGCs into ganglion-like cells, and excessive pressure can inhibit the differentiation of RSCs.
9.Effect of Parkinson′s disease factor on sedative efficacy of dexmedetomidine
Zefeng FAN ; Qiuyue FU ; Xiang LIU ; Chengwei YANG ; Mingming HAN ; Wanhong LI ; Juan LI ; Fang KANG
Chinese Journal of Anesthesiology 2022;42(11):1285-1288
Objective:To evaluate the effect of Parkinson′s disease factor on the sedative efficacy of dexmedetomidine.Methods:The patients of either sex, aged 45-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, with body mass index of 18.5-30.0 kg/m 2, undergoing non-intracranial space-occupying lesions in neurosurgery, were selected.Patients were divided into control group (group C) and Parkinson′s disease group (group P) according to whether they had Parkinson′s disease or not.The ED 50 of dexmedetomidine was determined by using the Dixon′s up-and-down method.The initial dose of dexmedetomidine was 0.5 μg/kg in both groups, and each time the concentration increased/decreased by 0.05 μg/kg in the next patient, which was repeated until 7th independent crossover pair (loss of consciousness) appeared, and then the test was ended.The ED 50 and 95% confidence interval of dexmedetomidine inducing loss of consciousness were calculated using the probit test in a Logistic regression model.Hypertension, hypotension, bradycardia and nausea and vomiting were recorded. Results:Compared with group C, the ED 50 of dexmedetomidine inducing loss of consciousness was significantly increased in group P ( P<0.05), and no significant change was found in the incidence of adverse reactions in group P ( P>0.05). Conclusions:Parkinson′s disease factor can decrease the sedative efficacy of dexmedetomidine.
10.Risk Factors for Duodenal Stump Leakage after Laparoscopic Gastrectomy for Gastric Cancer
Lihu GU ; Kang ZHANG ; Zefeng SHEN ; Xianfa WANG ; Hepan ZHU ; Junhai PAN ; Xin ZHONG ; Parikshit Asutosh KHADAROO ; Ping CHEN
Journal of Gastric Cancer 2020;20(1):81-94
PURPOSE:
Duodenal stump leakage (DSL) is a potentially fatal complication that can occur after gastrectomy, but its underlying risk factors are unclear. This study aimed to investigate the risk factors and management of DSL after laparoscopic radical gastrectomy for gastric cancer (GC).
MATERIALS AND METHODS:
Relevant data were collected from several prospective databases to retrospectively analyze the data of GC patients who underwent Billroth II (B-II) or Roux-en-Y (R-Y) reconstruction after laparoscopic gastrectomy from 2 institutions (Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and HwaMei Hospital, University of Chinese Academy of Sciences). The DSL risk factors were analyzed using univariate and multivariate analysis regression.
RESULTS:
A total of 810 patients were eligible for our analysis (426 with R-Y, 384 with B-II with Braun). Eleven patients had DSL (1.36%). Body mass index (BMI), elevated preoperative C-reactive protein (CRP) level, and unreinforced duodenal stump were the independent risk factors for DSL. DSL was diagnosed in 2–12 days, with a median of 8 days. Seven patients received conservative treatment, 3 patients received puncture treatment, and only 1 patient required reoperation. All patients recovered successfully after treatment.
CONCLUSIONS
The risk factors of DSL were BMI ≥24 kg/m², elevated preoperative CRP level, and unreinforced duodenal stump. Nonsurgical treatments for DSL are preferred.

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