1.Role of optic atrophy 1-mediated mitochondrial dynamics in the occurrence and development of central nervous system diseases
Gege QI ; Xingang DONG ; Weifeng LI ; Yan LIU ; Hui LI ; Yiqin REN ; Suqing ZHANG
Chinese Journal of Comparative Medicine 2025;35(4):104-113,134
Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.
2.Screening and preliminary evaluation of nanobodies targeting granulocyte-macrophage colony-stimulating factor
Jiao LIU ; Lei CHEN ; Hui QIN ; Qinlin KANG ; Gege LI ; Zhixin YANG ; Peng DU ; Chunyang ZHOU
Chinese Journal of Pharmacology and Toxicology 2025;39(8):591-599
OBJECTIVE To screen and obtain nanobodies with neutralizing activity against granulo-cyte-macrophage colony stimulating factor(GM-CSF)to contribute to investigations into the mecha-nism of inflammation interventions and the development new drugs.METHODS Recombinant human GM-CSF was subcutaneously injected to immunize camels.Peripheral blood was collected after five immunizations,and mononuclear cells were isolated.Total mRNA was extracted,and the variable domains of the heavy chain of heavy-chain antibody(VHH,also called nanobody)genes were obtained by PCR amplification after reverse transcription.The genes were cloned into the pADSCFV-S phage display vector and electrotransformed into TG1 competent cells to construct a nanobody immune library that was screened with recombinant human GM-CSF immobilized on a solid phase.The VHH genes specifi-cally binding to human GM-CSF were cloned into the pABG eukaryotic expression vector before VHH-Fc samples were prepared by using the human embryonic kidney 293 fibroblast expression system.The binding activity of candidate VHH-Fc molecules to GM-CSF was investigated through ELISA response curves,and binding colorimetric values with different antigens were detected to determine their specificity.The binding affinity between VHH-Fc candidates and GM-CSF was measured using biolayer interferom-etry(BLI).The inhibition rate curve of VHH-Fc candidates on GM-CSF was detected through cell prolif-eration assays to determine its neutralization activity.The Uncle system was used to investigate its thermal stability.100 μg of VHH-Fc was injected into mice via the tail vein,and the serum concentration of VHH-Fc was quantitatively detected by ELISA to examine its pharmacokinetic curve in mice.RESULTS The camel serum titer of anti-human GM-CSF antibodies was higher than 1:800 000 after the fifth immuni-zation,and the capacity of the constructed nanobody library was about 5.55×107.Following the screening process,five candidate VHH-Fc molecules specifically binding to human GM-CSF were obtained.Among these,22N10 effectively neutralized the cell proliferation-promoting activity of GM-CSF(the IC50 value was 17.23 nmol·L-1).Subsequent studies revealed that 22N10 interacted with human GM-CSF with an affinity of 1.97×10-8 mol·L-1,blocked the binding of GM-CSF to its receptor CSF2Rα,exhibited good thermal stability(Tm1=59.2℃),and showed favorable metabolic characteristics in mice.CONCLU-SION A new candidate nanobody molecule 22N10 targeting human GM-CSF is obtained which is expected to facilitate the drug development and mechanism investigations.
3.Research Progress of Botulinum Toxin Type A in the Treatment of Postherpetic Neuralgia
Fubo LI ; Gege GONG ; Yue ZHANG ; Cehua OU
Herald of Medicine 2025;44(8):1297-1302
Herpes zoster neuralgia(HZN)is a refractory neuropathic pain.Its incidence increases with age,along with higher prevalence of postherpetic neuralgia(PHN).The pain is severe and often lasts for months or even years,significantly impacting patients'work and life.How to reduce the pain level and prevent postherpetic neuralgia is the key to its treatment.However,conventional drug treatment often has adverse effects such as dizziness and drowsiness with low overall efficacy,which is not conducive to controlling and mitigating the pain.Botulinum toxin type A(BTX-A)is an exotoxin released by clostridium botulinum,which is simple to inject,and can effectively alleviate the pain level of PHN through mechanisms such as acting on synapses of neuromuscular junctions and inhibiting neuroinflammatory responses,thereby reducing the incidence of posterior neuralgia.This paper reviews the progress of BTX-A application in the diagnosis and treatment of PHN.
4.Effect of dexmedetomidine on TLR4/MyD88/NF-κB signaling pathway in hippocampus of mice with cognitive impairment after traumatic brain injury
Gege LYU ; Yudong SHAN ; Caoyuan MA ; Ruichao LI ; Limin ZHANG ; Wei ZHANG
Chinese Journal of Anesthesiology 2025;45(8):992-997
Objective:To evaluate the effect of dexmedetomidine on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in the hippocampus of mice with cognitive impairment after traumatic brain injury (TBI).Methods:Sixty specific pathogen-free healthy adult wild-type C57BL/6 mice, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=12 each) by a random number table method: sham operation + vehicle group (SV group), sham operation + dexmedetomidine group (SD group), TBI + vehicle group (TV group), TBI + dexmedetomidine group (TD group) and TBI + TLR4 inhibitor TAK-242 group (TT group). The modified Feeney free fall epidural impact method was used to establish a mild TBI model. At 30 min before model preparation, dexmedetomidine 25 μg/kg was intraperitoneally injected in SD group and TD group, TAK-242 10 mg/kg was intraperitoneally injected in TT group, and the equal volume of normal saline was intraperitoneally injected in SV group and TV group. Neurological severity scores (NSSs) were used to evaluate the neurological function at 1, 7 and 14 days after developing the model. The novel object recognition test (recognition index) and fear conditioning test (the percentage of freezing time related to context and sound) were used to evaluate the cognitive function of mice at 16 days after developing the model. The number and morphology of hippocampal neurons (NeuN-positive cells) and activated microglia (ionized calcium-binding adaptor molecule 1[IBA1]-positive cells) were measured by immunofluorescent staining. The expression of interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), TLR4, MyD88 and nuclear factor kappa B (NF-κB) was detected by Western blot. Results:Compared with SV group, the NSS was significantly increased, the recognition index was decreased, the percentage of freezing time related to context and sound was decreased, the number of NeuN-positive cells was decreased, the number of IBA1-positive cells was increased and the cell body area was enlarged, the total branch length and intersection points were decreased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was up-regulated in TV group ( P<0.05). Compared with TV group, the NSS was significantly decreased, the recognition index was increased, the percentage of freezing time related to context and sound was increased, the number of NeuN-positive cells was increased, the number of IBA1-positive cells was decreased and the cell body area was reduced, the total branch length and intersection points were increased, and the expression of TLR4, MyD88, NF-κB, IL-1β, IL-6 and TNF-α was down-regulated in TD group and TT group ( P<0.05). There was no statistically significant difference in the aforementioned parameters between TD group and TT group ( P>0.05). Conclusions:The mechanism by which dexmedetomidine mitigates TBI-induced cognitive impairment may be related to inhibition of the hippocampal TLR4/MyD88/NF-κB signaling pathway and reduction of neuroinflammatory responses in mice.
5.Study on the current situation and latent profile analysis of nurses'perceived organizational support
Jiangfeng PU ; Waner WANG ; Gege LI ; Zhanghao XIE ; Yixuan XU ; Ningjing ZHAN ; Huigen HUANG
Chinese Journal of Nursing 2025;60(3):340-347
Objective To analyze the cunent situation and latent profiles of nurses'perceived organizational support,and explore the influencing factors of different types.Methods Through convenience sampling,a total of 1,860 nurses from the Pearl River Delta,Northern Guangdong,Eastern Guangdong and Western Guangdong regions of Guangdong Province were selected for the survey between October and December 2023.The demographic questionnaire,the Perceived Organizational Support Scale,and the Psychological Resilience Scale were used for investigation.The latent profiles of the nurses'perceived organizational support,the influencing factors of latent profiles were identified by single-factor analysis and multivariate Logistic regression.Results The score of the items of the perceived organizational support in l,819 nurses is(3.47±0.88)scores.Nurses perceived organizational support is divided into 3 latent classes,namely"poor group"(10.1%),"balanced group"(44.4%),and"rich group"(45.5%).The influencing factors include recruitment type,hospital level,and psychological resilience(all P<0.05).Conclusion The perceived organizational support among nurses is moderately high and heterogeneous,which could be divided into 3 latent profiles.Nursing managers should focus on nurses from the poor group and balanced group and intervene with nurses according to the influencing factors of the different latent profiles to improve the level of nurses perceived organizational support.
6.Perineural invasion is an independent risk factor for poor prognosis of cervical cancer patients , and the occurrence of perineural invasion can be effectively predicted by the constructed multivariate mode.
Ran Tang ; Gege Jiang ; Xiangwen Meng ; Zheng Cai ; Li Jin ; Nan Xiang ; Min Zhang ; Xiaoyi Jia
Acta Universitatis Medicinalis Anhui 2025;60(12):2368-2377
Objective:
To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment.
Methods:
Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted.
Results:
Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses.
Conclusion
The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.
7.Development and application of chiral separation technology based on chiral metal-organic frameworks.
Gege ZHU ; Li GE ; Xinyu LI ; Bing NIU ; Qin CHEN ; Dan ZHONG ; Xiaodong SUN
Journal of Pharmaceutical Analysis 2025;15(7):101176-101176
Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.
8.Novel autosomal dominant syndromic hearing loss caused by COL4A2 -related basement membrane dysfunction of cochlear capillaries and microcirculation disturbance.
Jinyuan YANG ; Ying MA ; Xue GAO ; Shiwei QIU ; Xiaoge LI ; Weihao ZHAO ; Yijin CHEN ; Guojie DONG ; Rongfeng LIN ; Gege WEI ; Huiyi NIE ; Haifeng FENG ; Xiaoning GU ; Bo GAO ; Pu DAI ; Yongyi YUAN
Chinese Medical Journal 2025;138(15):1888-1890
9.Research Progress on the Correlation Between Mitophagy and Vascular Cognitive Impairment
Yan LIU ; Xingang DONG ; Xiaoyuan WANG ; Gege QI ; Yiqin REN ; Lianpeng ZHOU ; Hui LI ; Suqing ZHANG ; Weifeng LI
Medical Journal of Peking Union Medical College Hospital 2025;16(2):338-349
Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.
10.Study on the current situation and latent profile analysis of nurses'perceived organizational support
Jiangfeng PU ; Waner WANG ; Gege LI ; Zhanghao XIE ; Yixuan XU ; Ningjing ZHAN ; Huigen HUANG
Chinese Journal of Nursing 2025;60(3):340-347
Objective To analyze the cunent situation and latent profiles of nurses'perceived organizational support,and explore the influencing factors of different types.Methods Through convenience sampling,a total of 1,860 nurses from the Pearl River Delta,Northern Guangdong,Eastern Guangdong and Western Guangdong regions of Guangdong Province were selected for the survey between October and December 2023.The demographic questionnaire,the Perceived Organizational Support Scale,and the Psychological Resilience Scale were used for investigation.The latent profiles of the nurses'perceived organizational support,the influencing factors of latent profiles were identified by single-factor analysis and multivariate Logistic regression.Results The score of the items of the perceived organizational support in l,819 nurses is(3.47±0.88)scores.Nurses perceived organizational support is divided into 3 latent classes,namely"poor group"(10.1%),"balanced group"(44.4%),and"rich group"(45.5%).The influencing factors include recruitment type,hospital level,and psychological resilience(all P<0.05).Conclusion The perceived organizational support among nurses is moderately high and heterogeneous,which could be divided into 3 latent profiles.Nursing managers should focus on nurses from the poor group and balanced group and intervene with nurses according to the influencing factors of the different latent profiles to improve the level of nurses perceived organizational support.


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