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
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Retinal Ganglion Cells/metabolism*
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Glaucoma/pathology*
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Oxidative Stress/drug effects*
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Neuroprotective Agents/pharmacology*
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Mice
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Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
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Mice, Inbred C57BL
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Disease Models, Animal
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Neuroinflammatory Diseases/drug therapy*
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Neuroprotection/drug effects*
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Male
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Intraocular Pressure/drug effects*
2.Immunologic Features and Significance of Extramedullary Multiple Myeloma
Xiaosha LI ; Xiaohuan PENG ; Liansheng ZHANG
Journal of Medical Research 2025;54(8):63-67
Objective To study whether there are differences in immunological and hematological indexes in patients with extramed-ullary multiple myeloma(EMM).Methods The medical records of 150 newly diagnosed multiple myeloma(MM)patients admitted to Department of Hematology,the Second Hospital of Lanzhou University from January 2019 to January 2024 were retrospectively analyzed,to compare and analyze the differences in immunological and some hematological indexes between the EMM group(n=60)and the non-EMM group(n=90),and the two subgroups of the different risk stratification DS stages and Mayo myeloma risk stratification.Results The peripheral blood erythrocyte count,hemoglobin level,lactic acid dehydrogenase(LDH)level and interleukins-8(IL-8)levels of the patients in the EMM group were higher than those in the non-EMM group(P<0.05),the interleukins-10(IL-10)and the pro-portion of CD4+T cells in the EMM group were lower than those in the non-EMM group(P<0.05).Lymphocyte counts were signifi-cantly higher(P<0.05)and the proportion of CD8+T cells was significantly lower(P<0.05)in the EMM group of patients with stand-ard-risk MM.The proportion of peripheral blood CD8+T cells was significantly lower in the EMM group compared with the non-EMM group of patients with high-risk MM(P<0.05).LDH levels were higher in the EMM group than that in the non-EMM group in both DS-Ⅰ and DS-Ⅱ MM patients(P<0.05).Peripheral blood erythrocyte count,monocyte count,and hemoglobin level were higher in the EMM group than those in the non-EMM group in DS-Ⅲ MM patients(P<0.05).Conclusion Immune abnormalities may be one of the factors contributing to the occurrence,development and poor prognosis of EMM.This study suggest that CD8+T cells,as immune effector cells,can be further studied in the occurrence and progression of MM to EMM,providing a new basis for clinical treatment.
3.Concordance and pathogenicity of copy number variants detected by non-invasive prenatal screening in 38,611 pregnant women without fetal structural abnormalities.
Yunyun LIU ; Jing WANG ; Ling WANG ; Lin CHEN ; Dan XIE ; Li WANG ; Sha LIU ; Jianlong LIU ; Ting BAI ; Xiaosha JING ; Cechuan DENG ; Tianyu XIA ; Jing CHENG ; Lingling XING ; Xiang WEI ; Yuan LUO ; Quanfang ZHOU ; Ling LIU ; Qian ZHU ; Hongqian LIU
Chinese Medical Journal 2025;138(4):499-501
4.Application of optical surface monitoring system in intensity-modulated radiotherapy for thoracic tumors
Haixia YANG ; Menglu SUN ; Xiaosha ZHOU ; Yaxuan HAN ; Baolong REN ; Jianying LI ; Yi LI
The Journal of Practical Medicine 2025;41(9):1345-1351
Objective To evaluate the effect of optical body surface monitoring system(OSMS)in setup of intensity modulated radiotherapy(IMRT)for thoracic tumorsand to analyze its relationship with BMI.Methods Thesetup errors of CBCT and location CT with body membrane and the registration errors of OSMS and first body surface reference image without body membrane were obtained in 49 patients with thoracic tumor who received routine intensity modulated radiotherapy.The paired t-test was used to analyze the difference of registration errors between the two image guidance methods.Pearson′s correlation analysis was used to analyze the correlation between CBCT errors and OSMS errors,and Bland-Altman analysis was employed to evaluatethe agreement of the two errors.The correlation and consistency of the two registration errors in patients with different BMI index were analyzed.PTV external marginsby the two registration methods were calculated using Van Herk formula.Results The OSMS and CBCT groups demonstrated significant differences in setup errors in the ventrodorsal direction(P<0.05),while no significant differences were found in the left-right,head-foot translation directions,or RTN rota-tion directions(P>0.05).Although the two methods showed a significant correlation in setup errors(P<0.05),this correlation was only moderate in the head-foot and left-right directions(r=0.500,0.408),weak in the RTN rotation direction(r=0.339),and very weak in the ventrodorsal direction(r=0.152).The limits of agreement(LOA,95%CI)between the two methods were[-0.45,0.45]cm in the left-right direction,[-0.59,0.57]cm in the head-foot direction,and[-0.48,0.40]cm in the ventrodorsal direction,with(-2.08°~2.19°)in the RTN rotation direction.Different BMI levels influenced the results of the two registration methods,particularly in patients with a BMI of 18.5~23.9 kg/m2.In this group,OSMS and CBCT exhibited a strong correlation in the head-foot direction(r=0.731),a moderate correlation in the left-right direction(r=0.512),and weak correlations in the ventrodorsal and RTN rotation directions(r=0.345,0.267).The absolute difference in setup errors between the two imaging systems was 0.4~0.5 cm/2°.Using CBCT and OSMS image guidance,the margins in the left-right,head-foot,and ventrodorsal directions were[0.5 cm,0.7 cm,0.3 cm]for CBCT,and[0.5 cm,0.7 cm,0.5 cm]for OSMS.Conclusion In chest tumor patients with a BMI of 18.5~23.9 kg/m2,OSMS and CBCT image guidance methods show good correlation in the head-foot and left-right directions,but their limits of agreement exceed the clinically acceptable range.OSMS cannot yet replace CBCT for image guidance in chest tumor intensity-modulated radiotherapy.Further improvements to tumor motion surrogates are necessary to enhance the accuracy of OSMS image guidance.
5.Application of optical surface monitoring system in intensity-modulated radiotherapy for thoracic tumors
Haixia YANG ; Menglu SUN ; Xiaosha ZHOU ; Yaxuan HAN ; Baolong REN ; Jianying LI ; Yi LI
The Journal of Practical Medicine 2025;41(9):1345-1351
Objective To evaluate the effect of optical body surface monitoring system(OSMS)in setup of intensity modulated radiotherapy(IMRT)for thoracic tumorsand to analyze its relationship with BMI.Methods Thesetup errors of CBCT and location CT with body membrane and the registration errors of OSMS and first body surface reference image without body membrane were obtained in 49 patients with thoracic tumor who received routine intensity modulated radiotherapy.The paired t-test was used to analyze the difference of registration errors between the two image guidance methods.Pearson′s correlation analysis was used to analyze the correlation between CBCT errors and OSMS errors,and Bland-Altman analysis was employed to evaluatethe agreement of the two errors.The correlation and consistency of the two registration errors in patients with different BMI index were analyzed.PTV external marginsby the two registration methods were calculated using Van Herk formula.Results The OSMS and CBCT groups demonstrated significant differences in setup errors in the ventrodorsal direction(P<0.05),while no significant differences were found in the left-right,head-foot translation directions,or RTN rota-tion directions(P>0.05).Although the two methods showed a significant correlation in setup errors(P<0.05),this correlation was only moderate in the head-foot and left-right directions(r=0.500,0.408),weak in the RTN rotation direction(r=0.339),and very weak in the ventrodorsal direction(r=0.152).The limits of agreement(LOA,95%CI)between the two methods were[-0.45,0.45]cm in the left-right direction,[-0.59,0.57]cm in the head-foot direction,and[-0.48,0.40]cm in the ventrodorsal direction,with(-2.08°~2.19°)in the RTN rotation direction.Different BMI levels influenced the results of the two registration methods,particularly in patients with a BMI of 18.5~23.9 kg/m2.In this group,OSMS and CBCT exhibited a strong correlation in the head-foot direction(r=0.731),a moderate correlation in the left-right direction(r=0.512),and weak correlations in the ventrodorsal and RTN rotation directions(r=0.345,0.267).The absolute difference in setup errors between the two imaging systems was 0.4~0.5 cm/2°.Using CBCT and OSMS image guidance,the margins in the left-right,head-foot,and ventrodorsal directions were[0.5 cm,0.7 cm,0.3 cm]for CBCT,and[0.5 cm,0.7 cm,0.5 cm]for OSMS.Conclusion In chest tumor patients with a BMI of 18.5~23.9 kg/m2,OSMS and CBCT image guidance methods show good correlation in the head-foot and left-right directions,but their limits of agreement exceed the clinically acceptable range.OSMS cannot yet replace CBCT for image guidance in chest tumor intensity-modulated radiotherapy.Further improvements to tumor motion surrogates are necessary to enhance the accuracy of OSMS image guidance.
6.Immunologic Features and Significance of Extramedullary Multiple Myeloma
Xiaosha LI ; Xiaohuan PENG ; Liansheng ZHANG
Journal of Medical Research 2025;54(8):63-67
Objective To study whether there are differences in immunological and hematological indexes in patients with extramed-ullary multiple myeloma(EMM).Methods The medical records of 150 newly diagnosed multiple myeloma(MM)patients admitted to Department of Hematology,the Second Hospital of Lanzhou University from January 2019 to January 2024 were retrospectively analyzed,to compare and analyze the differences in immunological and some hematological indexes between the EMM group(n=60)and the non-EMM group(n=90),and the two subgroups of the different risk stratification DS stages and Mayo myeloma risk stratification.Results The peripheral blood erythrocyte count,hemoglobin level,lactic acid dehydrogenase(LDH)level and interleukins-8(IL-8)levels of the patients in the EMM group were higher than those in the non-EMM group(P<0.05),the interleukins-10(IL-10)and the pro-portion of CD4+T cells in the EMM group were lower than those in the non-EMM group(P<0.05).Lymphocyte counts were signifi-cantly higher(P<0.05)and the proportion of CD8+T cells was significantly lower(P<0.05)in the EMM group of patients with stand-ard-risk MM.The proportion of peripheral blood CD8+T cells was significantly lower in the EMM group compared with the non-EMM group of patients with high-risk MM(P<0.05).LDH levels were higher in the EMM group than that in the non-EMM group in both DS-Ⅰ and DS-Ⅱ MM patients(P<0.05).Peripheral blood erythrocyte count,monocyte count,and hemoglobin level were higher in the EMM group than those in the non-EMM group in DS-Ⅲ MM patients(P<0.05).Conclusion Immune abnormalities may be one of the factors contributing to the occurrence,development and poor prognosis of EMM.This study suggest that CD8+T cells,as immune effector cells,can be further studied in the occurrence and progression of MM to EMM,providing a new basis for clinical treatment.
7.Microenvironmental alterations and therapeutic advances in multiple myeloma bone disease
Yixin WEI ; Liansheng ZHANG ; Lijuan LI ; Xiaosha LI
Chinese Journal of Immunology 2024;40(5):1010-1015
Multiple myeloma bone disease(MBD)is a common clinical complication in patients with multiple myeloma(MM),and the occurrence of bone-related events seriously affects the quality of survival and prognosis of patients.The pathogenesis of MBD involves an imbalance in physiologic bone remodeling:overactivation of osteoclasts,suppression of osteoblasts,and multiple cell-cytokine interactions in the microenvironment,including osteoblasts,bone marrow stromal cells,and immune cells.The current treatment of MBD is based on standard antimyeloma therapy to control tumor progression,along with the use of bone-related drugs act-ing on bone remodeling within the indications.To prevent bone destruction.In order to prevent bone destruction,it is essential to in-duce new bone formation to repair the existing lesions while resisting bone resorption,and a variety of novel bone-targeting drugs are currently demonstrating anti-osteopathic effects in preclinical and clinical trials.This article summarizes new advances in the mecha-nisms of bone remodeling and treatment of MBD.
8.Advances in hypoxic tumor microenvironment-targeting mechanisms in multiple myel-oma treatment
Yixin WEI ; Liansheng ZHANG ; Xiaosha LI ; Lijuan LI
Chinese Journal of Clinical Oncology 2023;50(23):1227-1230
Multiple myeloma(MM)is a highly heterogeneous and refractory plasma cell tumor.It is similar to most solid tumors in the hyp-oxic tumor microenvironment(TME)it is exposed to,promoting hypoxia inducible factor-1(HIF-1)activation and related transcription factors of the corresponding downstream signaling pathways,affecting tumor angiogenesis,myeloma cell dissemination and metastasis,anti-tumor immunity,tumor immune escape promotion as well as altering the cellular energy metabolism and participating in therapeutic resistance in-duction.In this study,based on the above-described mechanisms,we aim at reviewing the current research status of hypoxic microenviron-ment-targeting therapies in MM treatment,focusing on the direct inhibition of HIF factors or signaling pathway targeting;metabolism im-provement and oxygenation increase;effective tumor immunity restoration by targeting immune checkpoints;anti-angiogenesis.Precise hypoxia targeting combined with standardized therapy offers a promising strategy and research hotspot in MM therapy.
9.Mobile-health information searching behaviors and its influencing factors for patients with cancer
Shuaini LI ; Wenyi HU ; Yating GAO ; Ying LIN ; Xiaosha NI ; Hemei WANG ; Yan LOU
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(5):426-433
Objective:To explore the behavior and influencing factors of mobile health (m-Health) information searching among patients with cancer, aiming to provide evidence for the provision of medical health information.Methods:A cross-sectional survey was conducted.A total of 535 patients with cancer were recruited from a cancer hospital in Zhejiang Province from September to December 2017.Measurement tools included the demographic information questionnaire, mobile health information search behavior questionnaire, mobile health information search environment questionnaire, cancer needs questionnaires-short form and ehealth literacy scale.SPSS 26.0 was used for descriptive statistical analysis, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis.Results:The total score of mobile health information search behavior of cancer patients was (60.84±9.60), and 66.5% of participants reported that they "never" or "occasionally" searched health information via mobile.The total score of information needs was (80.99±27.86), electronic health literacy was (26.54±7.85), mobile health information search environment was (8.00±2.86). m-Health information search behavior was positively correlated with information needs ( r=0.251, P<0.01), ehealth literacy ( r=0.538, P<0.01), and m-Health information search environment ( r=0.267, P<0.01). The stepwise regression analysis revealed that the place of residence, working status, income level, ehealth literacy, mobile health information search environment and information needs were statistically significant associated with the m-Health information searching behavior among cancer patients, which accounted for 39.3% of the total variance ( F=12.151, P<0.01). Compared with patients living in the central cities, those living in the small and medium-sized cities( β=0.092, P=0.031) had higher score in m-Health information behavior.Compared with patients working on normal schedule, those took sick days ( β=0.156, P=0.017) and working fewer hours ( β=0.138, P=0.002) had higher score m-Health information behavior.Compared with patients with monthly income of 1 000-3 000 yuan ( β=-0.194, P=0.002), those with monthly income less than 1 000 yuan had higher score in m-Health information behavior.The ehealth literacy ( β=0.425, P=0.000), mobile health information search environment ( β=0.179, P=0.000) and information needs ( β=0.091, P=0.027) were positive influencing factors of m-Health information search behavior. Conclusion:Patients with cancer did not report high m-Health information search behavior.Place of residence, working status, income level, ehealth literacy, m-Health information search environment and information demand were the influencing factors of m-Health information search behavior among patients with cancer.
10.Homocysteine and cerebral small vessel disease
Yifan JI ; Xiangyu LI ; Xiaosha LI ; Qiao YANG ; Yiyao SONG ; Haoyuan MA ; Peiyuan LYU
International Journal of Cerebrovascular Diseases 2020;28(2):134-139
Homocysteine participates in the methionine cycle in the body and is excreted by the kidneys. Its abnormal elevation increases the risk of cerebrovascular disease. Studies in recent years have shown that hyperhomocysteinemia is closely related to cerebral small vessel diseases and is an independent risk factor for ischemic stroke and cognitive impairment. Because hyperhomocysteinemia is largely reversible, the significance of drug intervention in the prevention and treatment of cerebrovascular disease has gradually been confirmed. This article reviews the relationship between homocysteine and cerebral small vessel diseases in order to provide a reference for the prevention of stroke and dementia.

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