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.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.
3.Efficacy of stented elephant trunk procedure for right-sided aortic arch with Kommerell's diverticulum
Yongliang ZHONG ; Bing TANG ; Suwei CHEN ; Yipeng GE ; Hai' ; ou HU ; Zhiyu QIAO ; Chengnan LI ; Yongmin LIU ; Junming ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):1020-1026
Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.
4.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.
5.Chinese expert consensus on targeted and immunotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer
Ping JIANG ; Zi LIU ; Lichun WEI ; Yunyan ZHANG ; Fengju ZHAO ; Xiangkun YUAN ; Yipeng SONG ; Jing BAI ; Xiaofan LI ; Baosheng SUN ; Lijuan ZOU ; Sha LI ; Yuhua GAO ; Yanhong ZHUO ; Song GAO ; Qin XU ; Xiaohong ZHOU ; Hong ZHU ; Junjie WANG
Chinese Journal of Radiation Oncology 2024;33(10):893-901
Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.
6.Comparative study of transfection of tumor antigen NY-ESO-1 circRNA with a novel cationic lipid-like material C1 to stimulate IFN-γ production in T cells
Hong ZHOU ; Yipeng MA ; Xiaojuan WANG ; Fenglan LIU ; Bin LI ; Dongjuan QIAO ; Xiaojun XIA ; Peigen REN ; Mingjun WANG
Chinese Journal of Microbiology and Immunology 2024;44(9):771-777
Objective:To express NY-ESO-1 epitopes using circular RNA (circRNA) and construct circRNA cancer vaccines using a novel lipid-like material C1, and to evaluate the transfection efficiency and T cell activation potential at cellular level.Methods:In vitro transcription was used to synthesize mRNA and circRNA expressing EGFP and NY-ESO-1 epitopes. Then, they were transfected into COS7 cells and the expression of target proteins were detected in vitro. Lipid-like material C1 and commercial transfection agent TransIT-mRNA were used as delivery systems for mRNA NY-ESO-1 and circRNA NY-ESO-1, and their delivery efficiency was compared. Results:The expression of EGFP was observed under fluorescence microscopy after transfection of mRNA EGFP and circRNA EGFP into COS7 cells for 24 h. The secretion of IFN-γ by T cell receptor-engineered T (TCR-T) cells targeting NY-ESO-1/HLA-A2 was stimulated by COS7-A*02: 01 cells transfected with mRNA NY-ESO-1 and circRNA NY-ESO-1. Compared with mRNA NY-ESO-1, circRNA NY-ESO-1 was able to express the target antigen and stimulate the target cells to release IFN-γ more persistently. The delivery efficiency of C1 material was better than that of commercial transfection reagents when COS7 cells were transfected in vitro. Conclusions:Compared with the linear mRNA, transfection of COS7-A*02: 01 cells with circRNA can lead to more efficient and durable activation of T cells, suggesting that it could be a more suitable candidate for clinical treatment of tumors in the future. The lipid-like material C1 can effectively deliver linear mRNA and circular RNA molecules. This study provides reference for further research on circRNA tumor vaccines.
7.The diagnostic value of serum anti-toxocara immunoglobulin G in ocular toxocariasis patients
Qing XU ; Chaoju GONG ; Xiao YANG ; Yalu LIU ; Jie LI ; Aiqin SHENG ; Yipeng ZHANG ; Lei QIAO ; Yanlian LI ; Suyan LI
Chinese Journal of Ocular Fundus Diseases 2024;40(5):366-371
Objective:To assess the diagnostic performance of serum anti-toxocara immunoglobulin G (anti-T-IgG) in ocular toxocariasis (OT) patients.Methods:A diagnostic tests. A total of 109 patients (109 eyes) with clinically-suspected OT who treated in Department of Ophthalmology of Xuzhou First People’s Hospital from June 2015 to December 2022 were included. Patients were divided into two groups, 76 with OT and 33 with non-OT, according to the clinical manifestations and Goldmann-Witmer coefficient. Paired serum and intraocular fluid samples from each patient were collected and analyzed for specific anti-T-IgG using enzyme linked immunosorbent assay. Mann-Whitney test was performed for comparison between groups. The area under the receiver operating characteristic curve (ROC) was used to assess the diagnostic performance of serum anti-T-IgG. Kappa analysis was performed to examine the consistency of serum or intraocular fluid anti-T-IgG positive rate with OT diagnostic result. Spearman’s rank correlation test was performed to assess the association.Results:Compared with the non-OT group, the proportions of children and history of exposure to cats and dogs ( χ2=9.785, 12.026) were significantly higher in OT group, and the differences were statistically significant ( P<0.01). The positive rate ( χ2=24.551) and U value ( Z=-4.379) of serum anti-T-IgG in OT group were higher than those in non-OT group, and the differences were statistically significant ( P<0.000 1). The recommended serum anti-T-IgG cut-off value of 11 U had 0.72 sensitivity, 0.79 specificity, 0.89 positive predictive value, 0.55 negative predictive value, and 0.77 area under the ROC with 95% confidence interval ( CI) 0.669-0.860. Correlation analysis showed that serum anti-T-IgG was positively correlated with intraocular fluid anti-T-IgG ( r s=0.520, 95% CI 0.363-0.648, P<0.000 1). The Kappa values of serum and intraocular fluid anti-T-IgG positive rate with OT diagnosis were 0.457 (95% CI 0.292-0.622) and 0.711 (95% CI 0.582-0.840), respectively. The Kappa value of serum anti-T-IgG positive rate with OT diagnosis was lower than that of intraocular fluid. Conclusion:The sensitivity and specificity of serum anti-T-IgG and the consistency between serum anti-T-IgG positive rate and OT diagnosis are low, suggesting that serum anti-T-IgG level cannot be used as a basis for OT diagnosis.
8.Osteotomy of non-core weight-bearing area of the lateral tibial plateau, reduction, and internal fixation in treatment of tibial plateau fractures involving posterolateral column collapse.
Xuan PEI ; Guodong WANG ; Shenglong QIAN ; Yipeng CHENG ; Zhixun FANG ; Xi KE ; Ximing LIU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(4):410-416
OBJECTIVE:
To investigate the effectiveness of osteotomy of non-core weight-bearing area of the lateral tibial plateau, reduction, and internal fixation in the treatment of tibial plateau fractures involving posterolateral column collapse.
METHODS:
A clinical data of 23 patients with tibial plateau fractures involving posterolateral column collapse, who had undergone osteotomy of non-core weight-bearing area of the lateral tibial plateau, reduction, and internal fixation between January 2015 and June 2021, was retrospectively analyzed. There were 14 males and 9 females with an average age of 42.6 years ranging from 26 to 62 years. The causes of injury included traffic accident in 16 cases, falling from height in 5 cases, and other injuries in 2 cases. According to Schatzker classification, there were 15 cases of type Ⅴ and 8 cases of type Ⅵ. The time from injury to operation was 4-8 days with an average of 5.9 days. The operation time, intraoperative blood loss, fracture healing time, and complications were recorded. The depth of articular surface collapse of posterolateral column and posterior inclination angle (PSA) of the tibial plateau were compared before operation and at 2 days and 6 months after operation; fracture reduction of tibial plateau fracture was evaluated by Rasmussen anatomic score. The recovery of knee function was evaluated by Hospital for Special Surgery (HSS) score at 2 days and 6 months after operation.
RESULTS:
All 23 patients were completed the operation successfully. The operation time was 120-195 minutes, with an average of 152.8 minutes; the intraoperative blood loss was 50-175 mL, with an average of 109.5 mL. All patients were followed up 12-24 months, with an average of 16.7 months. One patient had superficial wound infection after operation, and the incision healed after dressing change; primary healing of incision of other patients was obtained. The fracture healing time was 12-18 weeks, with an average of 13.7 weeks. No failure of internal fixation, varus and valgus deformity of the knee joint, and instability of the knee joint was found at last follow-up. One patient developed joint stiffness and the range of motion of the knee joint was 10°-100°; the range of motion of the knee joint of other patients was 0°-125°. At 2 days and 6 months after operation, the depth of articular surface collapse of posterolateral column, PSA, and Rasmussen anatomic scores significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two postoperative time points ( P>0.05). The HSS score at 6 months after operation was significantly higher than that at 2 days after operation ( P<0.05).
CONCLUSION
For tibial plateau fractures involving posterolateral column collapse, reduction and internal fixation through osteotomy of non-core weight-bearing area of the lateral tibial plateau has the advantages of fully expose the posterolateral column fragment, good articular surface reduction, sufficient bone grafting, and fewer postoperative complications. It is beneficial to restore knee joint function and can be widely used in clinic.
Male
;
Female
;
Humans
;
Adult
;
Retrospective Studies
;
Blood Loss, Surgical
;
Tibial Plateau Fractures
;
Treatment Outcome
;
Bone Plates
;
Tibial Fractures/surgery*
;
Knee Joint
;
Fracture Fixation, Internal
;
Osteotomy
;
Weight-Bearing
9.Qualitative studies on experience of the primary malignant bone tumors caregivers:a Meta-synthesis
Tao PENG ; Kaiqi HE ; Yipeng LEI ; Bingkun LI ; Xin LIU ; Linyu LAI ; Yumei ZHANG
Chinese Journal of Nursing 2023;58(22):2785-2791
Objective To systematically evaluate the qualitative studies on the care experience of caregivers for primary malignant bone tumors patients,in order to provide references for the construction of bone tumor support care system.Methods The Cochrane Library,PubMed,Embase,CNKI,Wanfang Database,VIP database,and China Biomedical Literature Database were searched by computer to collect qualitative studies on the care experience of caregivers of malignant bone tumors patients from the establishment of the databases to November 2022.The quality of the literature was evaluated using the Joanna Briggs Institute(JBI)Quality Evaluation Criteria for Quality Research in Evidence-Based Health Care Centers(2016),and the results were integrated by a pooled integration approach.Results A total of 12 studies were included;48 themes were extracted and summarized into 9 categories,which were combined into 3 integrated results.Integration result 1 is obvious physical and mental disturbance.Integration result 2 is multiple role maladaptation.Integration result 3 is positive growth after adjustment.Conclusion Caregivers of patients with malignant bone tumors have serious physical and mental burden and are eager for multiple support.It is suggested that medical staff pay attention to the multi-dimensional needs of patients,formulate personalized support strategies,help caregivers adapt and transform their roles,and promote the post-traumatic growth of caregivers.
10.Surgical analysis of anterior cervical approache in the treatment of brachial plexus schwannoma of thoracic outlet
Yipeng DONG ; Cang LIU ; Jing ZHANG ; Xianghua ZHANG
International Journal of Surgery 2023;50(11):752-756
Objective:To investigate the surgical treatment strategies of brachial plexus schwannomas protruding from the foraminal area to the thoracic outlet through anterior cervical approach, and to evaluate the curative effect.Methods:The clinical data of 8 patients treated in Beijing Friendship Hospital Affiliated to Capital Medical University from July 2016 to December 2020 who underwent supraclavicular cervical "barb" incision for protruding into the thoracic outlet through anterior cervical approach were retrospectively collected, including 5 males and 3 females, aged (50.75±11.14) years old, ranging from 31-66 years old. And the key points of the operation, postoperative complications and postoperative follow-up were analyzed. Measurement data with normal distribution were represented as mean±standard deviation( ± s), count data were described as numbers. Results:The tumors in all 8 cases were totally resected.The amount of bleeding during operation was (35.00±14.14) mL. No surgical complications such injury of pleura, aspneumothorax and hemothorax, except 2 cases which developed local sensory disturbance that improved that after neurotrophic treatment and hormonotherapy. All 8 patients were followed up by outpatient or telephone for 1-5 years, and cervical MRI review showed no tumor recurrence in situ.Conclusions:The anterior cervical approach with "barb type" incision above the neck clavicle is effective in excision of schwannomas protruding into the thoracic outlet, with less intraoperative injury, less blood loss, fast postoperative recovery.

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