1.HOCPCA Exerts Neuroprotection on Retinal Ganglion Cells by Binding to CaMKIIα and Modulating Oxidative Stress and Neuroinflammation in Experimental Glaucoma.
Panpan LI ; Xin SHI ; Hanhan LIU ; Yuan FENG ; Xiaosha WANG ; Marc HERB ; Haichao JI ; Stefan WAGNER ; Johannes VOGT ; Verena PROKOSCH
Neuroscience Bulletin 2025;41(8):1329-1346
Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals
;
Retinal Ganglion Cells/metabolism*
;
Glaucoma/pathology*
;
Oxidative Stress/drug effects*
;
Neuroprotective Agents/pharmacology*
;
Mice
;
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
;
Mice, Inbred C57BL
;
Disease Models, Animal
;
Neuroinflammatory Diseases/drug therapy*
;
Neuroprotection/drug effects*
;
Male
;
Intraocular Pressure/drug effects*
2.Immune-mediated neuropathies: pathophysiology and management
Yuxi TIAN ; Panpan YUAN ; Xingao WANG
Chinese Journal of Preventive Medicine 2024;58(9):1432-1437
Immune-mediated neuropathies (IMN) are a heterogenous group of disorders affecting the peripheral nervous system, due to dysregulation of the immune system. It mainly includes Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy and so on. Most of these diseases can be clinically improved by appropriate immunotherapy, but some patients still have unsatisfactory results. Therefore, studying the pathophysiology of the occurrence and development of diseases can reveal the nature of diseases and provide a theoretical basis for the prevention, diagnosis and treatment of diseases. In this paper, the pathophysiological mechanism of various IMNs is described in detail, with emphasis on immunological mechanism, and the progress of diagnosis and treatment of various IMNs is briefly introduced.
3.Exploration and practice based on internet+medical record copy service
Panpan XU ; Yuan TAO ; Yewen ZHAO
Modern Hospital 2024;24(9):1450-1452
Objective Based on the social background of digital development,the application value of Internet+medi-cal records copying and mailing is analyzed and summarized from the three levels of medical institutions,Internet companies and express delivery service companies.Methods Through literature research method,logical analysis method and other methods,the traditional copying method of medical record copying in a public hospital is logically analyzed,so as to obtain a more efficient Internet+medical record copying mode.Results The application of the Internet has a convenient,standardized and cost-saving effect on the copying of medical records,optimizes the service process,and improves the working efficiency of the medical record room.Conclusion The high-quality development of a public hospital needs to establish the patient privacy protection mechanism,play the Internet,establish the reliable database,play the sharing role of the Internet and establish the integration mechanism.
4.Prognosis and risk factors of IgA vasculitis nephritis in children
Xueqing MA ; Yonghua HE ; Jinyun PU ; Wenpei LIANG ; Panpan SHAO ; Jianhua ZHOU ; Yu ZHANG ; Jinhui TANG ; Tonglin LIU ; Huiqing YUAN ; Liru QIU
Chinese Journal of Pediatrics 2024;62(12):1184-1190
Objective:To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children.Methods:A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results:Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ2=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR=5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P=0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions:For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.
5.Effects of Yishen Huayu Xugu prescription combined with Dixumab on IL-6,β-CTX and bone mineral density in elderly patients operated for osteoporotic lumbar vertebral compression fractures
Bin ZHANG ; Wei HU ; Rongzhen TAN ; Panpan YANG ; Jun HU ; Zhong YUAN ; Gongtao JIANG
The Journal of Practical Medicine 2024;40(19):2766-2771
Objective To investigate the application value of Yishen Huayu Xugu prescriptionin the man-agement of osteoporotic lumbar compression fracture among elderly patients.Methods From March 2022 to August 2023,all elderly patients with osteoporotic lumbar compression fractures were enrolled in our hospital and randomly assigned into two groups.The patients were diagnosed with kidney deficiency and blood stasis syndrome through physical identification.After admission,both groups(85 cases each)underwent percutaneous kyphoplasty.The control group received conventional Western medicine treatment post-surgery,while the observation group was administered Yishen Huayu Xugu prescription.This herbal formula was prepared by decocting 300 mL of juice in water,divided into two doses,and taken warmly after breakfast and dinner for a duration of 12 weeks.Therapeutic effects were compared after completion of the 12-week treatment period.Results After treatment,the serum levels of D-dimer(D-dimer,D-D)were(5.02±0.63),interleukin-17(IL-17)was(53.68±5.47),β-collagen special sequence(β-CTX)was(0.37±0.06,interleukin-6(IL-6)was(69.38±8.27)compared to the control group;bone morphogenetic protein-2(BMP-2)was(2.69±0.31),25-hydroxyvitamin D was(58.93±7.17),and vascular endo-thelial growth factor(VEGF)was(309.81±51.49)which were higher than those in the control group with more sig-nificant improvement observed in the intervention group(P<0.05).Bone mineral density(BMD)increased at both week 6 and week12 after treatment with a more pronounced improvement seen in the intervention group(P<0.05).After treatment,the observation group exhibited a more significant reduction in the total Traditional Chinese Medicine(TCM)symptom score,Cobb Angle,and ODI,compared to the control group(P<0.05).Furthermore,the observation group demonstrated a higher total effective rate of 95.29%(81/85)compared to 85.88%(73/85)in the con-trol group after treatment,with a statistically significant difference between the two groups(P<0.05).Conclusion The Yishen Huayu Xugu prescription holds significant positive implications for this particular medication,as it ex-hibits enhanced efficacy in reducing inflammation,regulating bone metabolism,improving lumbar function,promot-ing disease amelioration,and enhancing clinical outcomes.
6.Immune-mediated neuropathies: pathophysiology and management
Yuxi TIAN ; Panpan YUAN ; Xingao WANG
Chinese Journal of Preventive Medicine 2024;58(9):1432-1437
Immune-mediated neuropathies (IMN) are a heterogenous group of disorders affecting the peripheral nervous system, due to dysregulation of the immune system. It mainly includes Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy and so on. Most of these diseases can be clinically improved by appropriate immunotherapy, but some patients still have unsatisfactory results. Therefore, studying the pathophysiology of the occurrence and development of diseases can reveal the nature of diseases and provide a theoretical basis for the prevention, diagnosis and treatment of diseases. In this paper, the pathophysiological mechanism of various IMNs is described in detail, with emphasis on immunological mechanism, and the progress of diagnosis and treatment of various IMNs is briefly introduced.
7.Discovery of novel small molecules targeting hepatitis B virus core protein from marine natural products with HiBiT-based high-throughput screening.
Chao HUANG ; Yang JIN ; Panpan FU ; Kongying HU ; Mengxue WANG ; Wenjing ZAI ; Ting HUA ; Xinluo SONG ; Jianyu YE ; Yiqing ZHANG ; Gan LUO ; Haiyu WANG ; Jiangxia LIU ; Jieliang CHEN ; Xuwen LI ; Zhenghong YUAN
Acta Pharmaceutica Sinica B 2024;14(11):4914-4933
Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC50 = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.
8.Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review.
Xueli JIN ; Hui LIU ; Jing LI ; Xibin XIAO ; Xianggui YUAN ; Panpan CHEN ; Boxiao CHEN ; Yun LIANG ; Fengbo HUANG
Journal of Zhejiang University. Science. B 2023;24(8):711-722
Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
Humans
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Rituximab/therapeutic use*
;
Vincristine/therapeutic use*
;
Prednisone/therapeutic use*
;
Epstein-Barr Virus Infections/drug therapy*
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Herpesvirus 4, Human
;
Neoplasm Recurrence, Local
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Lymphoma, T-Cell/drug therapy*
;
Cyclophosphamide/therapeutic use*
;
Lymphoma, Large B-Cell, Diffuse/pathology*
;
Doxorubicin/therapeutic use*
;
Lymphadenopathy/drug therapy*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
9.Effects of early activity based on action research method in severely ill children
Meng YUAN ; Bo ZHANG ; Qian LI ; Xiaoxia SHI ; Panpan DING ; Xiaoxiao WANG ; Li ZHANG ; Caixia MA
Chinese Journal of Modern Nursing 2023;29(7):940-944
Objective:To explore the effect of early activity based on action research method in severely ill children.Methods:From February 2020 to January 2022, 101 children with severe illness admitted to the Henan Provincial People's Hospital were selected as the study subjects by convenient sampling. The 51 children with severe illness included from February 2020 to January 2021 were set as the control group, and the 50 children with severe illness included from February 2021 to January 2022 were set as the experimental group. The children in the control group were treated with routine rehabilitation in the Pediatric Intensive Care Unit (PICU) , and the experimental group was treated with early activity based on action research method on the basis of the control group. Before and after the intervention, the effect was evaluated by the Medical Research Council Scale (MRC) , the Intensive Care Unit Mobility Scale (IMS) , the length of stay in PICU and hospitalization time, and the incidence of ICU-acquired weakness (ICU-AW) when transferring out of PICU.Results:When transferring out of PICU, the MRC muscle strength score of children in the experimental group was higher than that in the control group, and the incidence of ICU-AW was lower than that in the control group, and the difference was statistically significant ( P<0.05) . After intervention, the IMS score of children in the experimental group was higher than that in the control group, and the difference was statistically significant ( P<0.05) . The length of stay in PICU and hospitalization time of children in the experimental group were shorter than those in the control group with statistical differences ( P<0.05) . Conclusions:Early activity based on action research method can effectively prevent the occurrence of ICU-AW in severely ill children, improve the activity of children, and shorten the hospitalization time, which is worthy of clinical promotion and application.
10.I n situ synthesis and unidirectional insertion of membrane proteins in liposome-immobilized silica stationary phase for rapid preparation of microaffinity chromatography.
Yanqiu GU ; Rong WANG ; Panpan CHEN ; Shengnan LI ; Xinyi CHAI ; Chun CHEN ; Yue LIU ; Yan CAO ; Diya LV ; Zhanying HONG ; Zhenyu ZHU ; Yifeng CHAI ; Yongfang YUAN ; Xiaofei CHEN
Acta Pharmaceutica Sinica B 2022;12(9):3682-3693
Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl4-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

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