1.Application of Mitophagy in Regulating Ulcerative Colitis Based on "Spleen Dysfunction in Essence Distribution Leading to Endogenous Turbid Pathogens"
Xuli YANG ; Yanwei HAO ; Qiaobo YE ; Lingling YUAN ; Ruijie FANG ; Yi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):176-184
Ulcerative colitis (UC) is a chronic, non-specific intestinal inflammatory disease. Its pathogenesis is complex, involving interactions among genetic, immune, and environmental factors, and remains incompletely elucidated. Mitochondrial damage can trigger the abnormal release of mitochondrial damage-associated molecular patterns (mtDAMPs), activating inflammatory pathways and thereby exacerbating the inflammatory response in UC. Mitophagy, a core mitochondrial quality control mechanism, can clear damaged mitochondria and effectively reduce the abnormal release of mtDAMPs and the accumulation of harmful substances, thereby mitigating inflammatory damage resulting from mitochondrial dysfunction. Mitophagy plays a crucial role in maintaining the integrity of the intestinal epithelial barrier function and in the prevention and intervention of UC. Notably, the function of the spleen governing transportation and transformation in traditional Chinese medicine shares similarities with the role of mitochondria in energy transformation and substance metabolism. Furthermore, the pathological state of the spleen failing in transportation and transformation may be related to mitochondrial dysfunction, while the pathogenic characteristics of "endogenous turbid pathogen" align with the inflammatory cascade responses triggered by abnormal release of mtDAMPs. Based on this theoretical correlation, this paper aims to explore the correlation between the traditional Chinese medicine theory of "spleen dysfunction in essence distribution leading to endogenous turbid pathogens" and mitophagy. Using the correlation as an entry point, the potential role of mitophagy in the pathogenesis of UC was elucidated. Additionally, by considering the epidemiological characteristics of UC in the Southwest region of China, a new thinking for the treatment of UC from the perspective of turbid pathogens was proposed based on the "fortifying the spleen and resolving turbidity" method to provide theoretical support and research enlightenment for further exploring the prevention and treatment of UC with traditional Chinese medicine.
2.Influencing factors for calcium salt deposition in patients with alveolar echinococcosis
Zitong XIONG ; Zhiyi LIN ; Yanxin HUANG ; Fuzhong FANG ; Zhengzhan WU ; Zirui XIN ; Chunxia HU ; Jiayu ZHOU ; Yuan YAO ; Hongwei ZHANG
Journal of Clinical Hepatology 2026;42(2):372-379
ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis, as well as independent risk factors for the degree of calcium salt deposition in lesions, and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025, and according to the volume of calcium salt deposition, they were divided into non-deposition group with 16 patients, mild deposition group with 52 patients, moderate deposition group with 16 patients, and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups, and the χ2 test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group (no/mild deposition) and the high deposition group (moderate/severe deposition). A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition, and a predictive model was established. The receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model, and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.05). The univariate analysis showed that there were significant differences between the four groups in sex, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, alanine aminotransferase, albumin, creatinine, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.1). The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760, suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex, involvement of other sites, calcium ion, lymphocyte percentage, and uric acid. The multivariate analysis showed that lymphocyte percentage (odds ratio [OR]=1.106, 95% confidence interval [CI]: 1.041 — 1.174, P=0.001) and blood calcium level (OR=0.005, 95%CI: 0.000 —0.230, P=0.007) were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit(P)=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716, with a Youden index of 0.353, a sensitivity of 1.000, and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration (χ2=20.688, P=0.008). The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage (OR=1.106, 95%CI: 1.049 — 1.186, P=0.002) and calcium ion (OR=0.005, 95%CI: 0.000 — 0.214, P=0.010) were consistent with the original model, and the confidence intervals did not include 1, which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis, and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.
3.Species of sandflies and prevalence of Leishmania infections in sandflies in selected areas of northern and northwestern China
Yaqi HE ; Lei CUI ; Yi ZHANG ; Yuanyuan LI ; Limin YANG ; Yuan FANG ; Zhongqiu LI ; Zhengbin ZHOU
Chinese Journal of Schistosomiasis Control 2026;38(1):20-28
Objective To investigate the species of sandflies and the prevalence of Leishmania infections in sandflies from selected areas of northern and northwestern China, so as to provide insights into identification of leishmaniasis vectors and assessment of epidemiological trends of leishmaniasis in China. Methods Sandfly samples were collected from Mentougou District of Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County of Karamay District of Karamay City, Gaochang District of Turpan City in Xinjiang Uygur Autonomous Region from July 2023 to July 2024. Approximately 100 intact female sandfly samples were randomly selected from each site and the species of sandflies was identified according to morphological characteristics and molecular assays. Female sandflies originating from the same habitat were grouped into pools of 10 individuals. Leishmania infection was detected using polymerase chain reaction (PCR) assay targeting the internal transcribed spacer 1 (ITS-1) gene, and the prevalence of Leishmania infection was calculated in sandflies from different sampling sites using the minimum infection rate (MIR) method. In addition, positive amplicons were sequenced and subjected to phylogenetic analysis. Results A total of 6 155 sandflies were collected from different environments at sampling sites across the six aforementioned regions from July 2023 to July 2024. Phlebotomus chinensis (96.00%) was the dominant sandfly species in Mentougou District, Beijing Municipality, with a small proportion of Ph. sergenti (4.00%), and only Ph. chinensis was found in Xiangning County, Linfen City, Shanxi Province. Ph. wui was the only sandfly species detected in Ejin Banner, Alxa League, Inner Mongolia Autonomous Region, and Payzawat County, Kashgar City, Xinjiang Uygur Autonomous Region, and Ph. caucasicus (97.70%) was the dominant sandfly species in Karamay District, Karamay City, Xinjiang Uygur Autonomous Region, with a small proportion of Ph. wui (2.30%), while Ph. alexandri was the only species in Gaochang District, Turpan City, Xinjiang Uygur Autonomous Region. A total of 40, 60, 34, 18, 18, and 22 pools of sandfly samples were tested from Mentougou District in Beijing Municipality, Xiangning County in Linfen City of Shanxi Province, Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, Payzawat County in Kashgar City, Karamay District in Karamay City, and Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region, respectively. L. infantum was detected in Ph. chinensis samples from Mentougou District in Beijing Municipality, and Xiangning County of Linfen City in Shanxi Province, with MIR of 0.25% to 1.00%, and L. donovani was detected in Ph. wui from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region, and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region, with MIR of 0.56% to 0.88%; however, no Leishmania infection was detected in Ph. caucasicus from Karamay District in Karamay City or Ph. alexandri from Gaochang District in Turpan City of Xinjiang Uygur Autonomous Region. Phylogenetic analysis showed that the Leishmania ITS-1 gene sequences obtained from Mentougou District in Beijing Municipality and Xiangning County in Linfen City of Shanxi Province were clustered into the same clade with the reference sequences of L. infantum ITS-1 gene, while the Leishmania ITS-1 gene sequences obtained from Ejin Banner in Alxa League of Inner Mongolia Autonomous Region and Payzawat County in Kashgar City of Xinjiang Uygur Autonomous Region were clustered into the same clade with the reference sequences of L. donovani ITS-1 gene. Conclusions There are variations in sandfly species in selected areas of northern and northwestern China, and variations in the species of Leishmania infecting sandflies. Improved surveillance of sandfly vectors and targeted control strategies with adaptations to geographical features and leishmaniasis vectors are recommended.
4.The current situation, challenges, and system construction of standardized training of transfusion technicians for blood service
Yuan FANG ; Xiaoyan NI ; Lili ZHANG ; Ye YANG ; Wei SHEN
Chinese Journal of Blood Transfusion 2026;39(7):963-966
Transfusion technicians constitute a core workforce in safeguarding blood safety, and the quality of their standardized training directly affects the operational efficiency of the blood services. At present, training programs for transfusion technicians across China have been developed in a diversified manner. Positive progress has been achieved in integrated theoretical and practical training, on-the-job faculty development, and regional collaborative training models. However, persistent challenges remain, including fragmented training providers, inconsistent training standards, limited coverage, and a disconnect between training and workforce utilization. Based on a review of current standardized training practice, this article systematically analyzes the structural challenges confronting current standardized training, and further proposes a framework for building a comprehensive training system, covering the definition and core components of standardized training, targeted improvement strategies and key assessment indicators. The study aims to facilitate the transformation of training for blood transfusion technicians in blood services from a project-based approach to an institutionalized model, and from fragmented implementation to a systematic framework.
5.Construction and validation of a predictive model based on the features of ultrasound imaging omics at the area peripheral thyroid nodule for the status of cervical lymph nodule of papillary thyroid carcinoma
Jinyan YANG ; Yuan FANG ; Kaiyuan ZHANG ; Wensi QIANG ; Xinmei ZHANG
China Medical Equipment 2025;22(11):74-80
Objective:To explore the efficacy of the features of ultrasound imaging omics at the area peripheral thyroid nodule in predicting cervical lymph node metastasis(LNM)of papillary thyroid carcinoma(PTC),and construct a prediction model based on the features of imaging omics and to verify its performance.Methods:A total of 237 PTC patients who admitted to Shaanxi Provincial Hospital of Chinese Medicine from March 2021 to June 2024 and were confirmed by pathology were retrospectively collected.They were divided into the training set(166 cases)and the validation set(71 cases)as a ratio of 7 to 3.According to the postoperatively pathological results,237 patients were divided into the metastasis group(108 cases)and the non-metastasis group(129 cases).The clinical data and conventional ultrasound characteristic information of all patients were collected,and a feature model of imaging omics was constructed through quantitative extracting and screening the features of ultrasound imaging omics within nodules and peripheral nodules,and utilizing machine learning classifier.Then,the feature score(Rad-Score)of image omics was obtained.The Rad-Score values within and peripheral nodules,and the Rad-Score values peripheral nodules of metastasis group and non-metastasis group were compared.In training set,the independent risk factors of affecting neck LNM were analyzed,and a clinical-ultrasonic model was constructed,which was combined with Rad-Score to construct a joint model based on the features of imaging omics peripheral nodules.The receiver operating characteristic(ROC)curve was used to analyze and compare its predictive efficacy.The nomogram of the joint model was constructed,and then,the calibration and fitting degrees of the nomogram were assessed by calibration curve and Hosmer-Lemeshow test.Result:In training set,6 features of imaging omics within nodules and 11 features of imaging omics peripheral nodules were respectively extracted and screened out through the least absolute shrinkage and selection operator(LASSO)algorithm.In the training set and validation set,the Rad-Scores peripheral the nodules in the metastasis group were respectively(7.43±0.45)points and(7.19±0.51)points,which were significantly higher than(3.25±0.28)points and(3.51±0.32)points peripheral the nodules in the non-metastasis group,and the differences were statistically significant(t=72.708,61.222,P<0.05).The results of factor analysis showed that age,capsule invasion,microcalcification,ultrasound-indicated lymph node positivity and Rad-Score around nodules were independent risk factors of affecting cervical LNM of PTC patients(OR=0.592,2.983,3.593,4.424,2.575,P<0.05).The ROC curve showed that the area under curve(AUC)values of the ROC curve of joint model in training set and validation set were respectively 0.861 and 0.872 in predicting LNM,respectively,which were superior to 0.759 and 0.783 of the clinical-ultrasound model.Conclusion:In both the training set and the validation set,the nomogram of joint model has favorable calibration and fitting in predicting cervical LNM of PTC patients.The construction of clinical model based on the features of ultrasound imaging omics peripheral nodules has a favorable efficacy in predicting the status of cervical lymph node of PTC patients before surgery,which is expected to be an effective tool of individual prediction for LNM.
6.Dental Floss-derived Biological Sample Collection,DNA Extraction and STR Typing
Ze-Qin LI ; Fang YUAN ; Na LIU ; Jiang-Wei YAN ; Geng-Qian ZHANG
Journal of Forensic Medicine 2025;41(3):237-243
Objective To evaluate the forensic application value of used dental floss as a source of bio-logical evidence for individual identification by analyzing the effects of dental floss sample collection methods,DNA extraction methods,preservation conditions,and sampling sites on the success rate of STR typing.Methods Dental floss samples were collected using three techniques:direct cutting,cotton swab wiping,and flocked swab wiping,respectively.DNA was extracted respectively by the Chelex,spin column-based and magnetic bead-based methods.DNA quantification and STR typing were per-formed using the Qubit kit and FGI HumDNA Typing kit(Platinum),respectively.Storage environ-ments(temperature and humidity,ultraviolet radiation)and sampling locations(the floss part,the handle part)on DNA quantity and STR typing were evaluated.Results Through conducting a statisti-cal analysis of three key indicators of average DNA mass concentration,STR locus detection rate,and typing accuracy rate,the direct cutting method demonstrated the highest efficacy,followed by cotton swab wiping mothed,and the flocked swab wiping method had the lowest efficacy.Direct cutting yielded an average DNA mass concentration greater than(4.94±1.87)ng/μL,with STR locus detection and accuracy rates of 100%.Bead-based DNA extraction method produced superior DNA concentration and quality compared to spin column-based and Chelex methods,regardless of whether the sampling technique used.Preservation conditions had a significant impact on the DNA analysis of samples.Par-ticularly,the STR typing accuracy of samples preserved at 55℃/50%RH for 35 days dropped to(81.82±12.31)%,and that of samples exposed to ultraviolet radiation for 12 h dropped to(55.46±34.31)%.DNA concentration from the handle part of dental floss was extremely low,with an STR typing accuracy of only(30.91±27.35)%.Conclusion Using cotton swabs to wipe or directly cutting the thread of dental floss samples,and combining this approach with the magnetic bead method for DNA extraction,can best guarantee the concentration and quality of DNA.In addition,samples should be stored in low-temperature,low-humidity environment,protected from light and ultraviolet radiation.
7.Risk prediction model for long-term visual acuity recovery in macular edema secondary to branch retinal vein occlusion patients after combination therapy
Chinese Journal of Postgraduates of Medicine 2025;48(7):628-634
Objective:To analyze the possible factors affecting the long-term visual acuity of macular edema secondary to branch retinal vein occlusion (BRVO-ME) after combination therapy, and construct a risk prediction model.Methods:The data of 125 patients with BRVO-ME who were treated in Xi′an Aier Ancient City Eye Hospital from December 2020 to December 2023 and completed 6-month follow-up were retrospectively analyzed. All patients were treated with ranibizumab combined with dexamethasone intravitreal implants until the central macular thickness returned to normal. The treatment was completed and followed up for 6 months. According to the 6-month follow-up of long-term visual acuity recovery, they were divided into poor recovery group (38 cases) and good recovery group (87 cases). The general data of the two groups were collected and compared. The possible influencing factors (continuous variables) were included in the drawing of the receiver operating characteristic (ROC) curve. According to the optimal threshold, the continuous variables were divided into two categorical variables, and the possible influencing factors were further included in the Logistic regression to obtain the possible influencing factors. Based on the results of the influencing factor analysis and the ROC curve, the decision curve was drawn to verify the clinical benefit of the overall model. Based on the above-mentioned nomogram model, the prediction model was visualized.Results:The course of disease in the poor recovery group was longer than that in the good recovery group: (82.47 ± 15.51) d vs. (71.23 ± 12.45) d, the proportion of ellipsoid/external membrane interruption was higher than that in the good recovery group: 44.74% (17/38) vs. 25.29% (22/87), the initial visual acuity was worse than that in the good recovery group: (0.82 ± 0.21) logMAR vs. (0.66 ± 0.17) logMAR, and the ratio of retinal deep and shallow blood flow density was lower than that in the good recovery group: 1.02 ± 0.35 vs. 1.36 ± 0.41, the difference was statistically significant ( P<0.05). ROC curve analysis showed that the area under the curve of the course of disease, the initial visual acuity, and the ratio of retinal deep and shallow blood flow density to predict the poor recovery of long-term visual acuity in BRVO-ME patients after combined medication were 0.71, 0.73 and 0.75, respectively. The best cut-off values were 85 d, 0.72 logMAR and 1.10, respectively. Logistic regression analysis showed that the course of disease (≥ 85 d), ellipsoid/outer membrane interruption (yes), initial visual acuity (≥ 0.72 logMAR) and ratio of retinal deep and shallow blood flow density (≤1.10) were the influencing factors of poor long-term visual acuity recovery in BRVO-ME patients after combination therapy ( P<0.05). The risk prediction model was constructed by using the course of disease, ellipsoid/outer membrane interruption, initial visual acuity and ratio of retinal deep and shallow blood flow density as predictors, and the decision curve of the model was drawn. It was found that the risk threshold was in the range of 0 to 0.90 and 0.95 to 1.00, and the clinical net benefit rate provided by the model was always greater than 0. The nomogram model was constructed to visualize the risk prediction model. The results showed that the C-index of the model to predict the long-term visual acuity recovery of BRVO-ME patients after combination therapy was 0.90 (95% CI 0.85 to 0.96), which had high predictive value. Conclusions:The course of the disease, interruption of the ellipsoid/outer membrane, initial visual acuity and the ratio of retinal deep and shallow blood flow density are all influencing factors for poor long-term visual recovery in BRVO-ME patients after combination therapy. The risk prediction model constructed based on this has good predictive value for the risk of poor long-term visual recovery in patients.
8.Mechanism of Mongolian medicine Echinops sphaerocephalus L.in proliferation and angiogenesis of vascular endothelial cells
Yuan FANG ; Zhiyong QIAN ; Yuanhada HE ; Haiyan WANG ; Lirong SHA ; Xiaohe LI ; Jing LIU ; Yachao HE ; Kai ZHANG ; TEMRIBAGEN
Chinese Journal of Tissue Engineering Research 2025;29(35):7519-7528
BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.
9.Buqi-Tongluo Decoction inhibits osteoclastogenesis and alleviates bone loss in ovariectomized rats by attenuating NFATc1, MAPK, NF-κB signaling.
Yongxian LI ; Jinbo YUAN ; Wei DENG ; Haishan LI ; Yuewei LIN ; Jiamin YANG ; Kai CHEN ; Heng QIU ; Ziyi WANG ; Vincent KUEK ; Dongping WANG ; Zhen ZHANG ; Bin MAI ; Yang SHAO ; Pan KANG ; Qiuli QIN ; Jinglan LI ; Huizhi GUO ; Yanhuai MA ; Danqing GUO ; Guoye MO ; Yijing FANG ; Renxiang TAN ; Chenguang ZHAN ; Teng LIU ; Guoning GU ; Kai YUAN ; Yongchao TANG ; De LIANG ; Liangliang XU ; Jiake XU ; Shuncong ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):90-101
Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals
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NFATC Transcription Factors/genetics*
;
Drugs, Chinese Herbal/pharmacology*
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Ovariectomy
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Osteoclasts/metabolism*
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Female
;
Osteogenesis/drug effects*
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Rats, Sprague-Dawley
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Rats
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NF-kappa B/genetics*
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Osteoporosis/genetics*
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Signal Transduction/drug effects*
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Bone Resorption/genetics*
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Cell Differentiation/drug effects*
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Humans
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RANK Ligand/metabolism*
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Mitogen-Activated Protein Kinases/genetics*
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Transcription Factors
10.Nogo-A Protein Mediates Oxidative Stress and Synaptic Damage Induced by High-Altitude Hypoxia in the Rat Hippocampus.
Jin Yu FANG ; Huai Cun LIU ; Yan Fei ZHANG ; Quan Cheng CHENG ; Zi Yuan WANG ; Xuan FANG ; Hui Ru DING ; Wei Guang ZHANG ; Chun Hua CHEN
Biomedical and Environmental Sciences 2025;38(1):79-93
OBJECTIVE:
High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear.
METHODS:
In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models.
RESULTS:
Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure.
CONCLUSION:
Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure.
GRAPHICAL ABSTRACT
available in www.besjournal.com.
Animals
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Oxidative Stress
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Hippocampus/metabolism*
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Rats
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Nogo Proteins/genetics*
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Male
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Rats, Sprague-Dawley
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Hypoxia/metabolism*
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Altitude
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Synapses
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Humans
;
Altitude Sickness/metabolism*

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