1.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
;
Oxidative Stress
;
Hippocampus/metabolism*
;
Rats
;
Nogo Proteins/genetics*
;
Male
;
Rats, Sprague-Dawley
;
Hypoxia/metabolism*
;
Altitude
;
Synapses
;
Humans
;
Altitude Sickness/metabolism*
2.Prevalence and treatment of anemia in chronic kidney disease patients based on regional medical big data.
Yang Fan CHAI ; Hong Bo LIN ; Guo Hui DING ; Jin Wei WANG ; Huai Yu WANG ; Su Yuan PENG ; Bi Xia GAO ; Xin Wei DENG ; Gui Lan KONG ; Bei Yan BAO ; Lu Xia ZHANG
Chinese Journal of Epidemiology 2023;44(7):1046-1053
Objective: To assess the prevalence, risk factors and treatment of anemia in patients with chronic kidney disease (CKD). Methods: A descriptive method was used to analyze the prevalence and treatment of anemia in CKD patients based on regional health data in Yinzhou District of Ningbo during 2012-2018. The multivariate logistic regression analysis was used to identify independent influence factors of anemia in the CKD patients. Results: In 52 619 CKD patients, 15 639 suffered from by anemia (29.72%), in whom 5 461 were men (26.41%) and 10 178 were women (31.87%), and anemia prevalence was higher in women than in men, the difference was significant (P<0.001). The prevalence of anemia increased with stage of CKD (24.77% in stage 1 vs. 69.42% in stage 5, trend χ2 test P<0.001). Multivariate logistic regression analysis revealed that being women (aOR=1.57, 95%CI: 1.50-1.63), CKD stage (stage 2: aOR=1.10, 95%CI: 1.04-1.16;stage 3: aOR=2.28,95%CI: 2.12-2.44;stage 4: aOR=4.49,95%CI :3.79-5.32;stage 5: aOR=6.31,95%CI: 4.74-8.39), age (18-30 years old: aOR=2.40,95%CI: 2.24-2.57, 61-75 years old: aOR=1.35,95%CI:1.28-1.42, ≥76 years old: aOR=2.37,95%CI:2.20-2.55), BMI (<18.5 kg/m2:aOR=1.29,95%CI: 1.18-1.41;23.0-24.9 kg/m2:aOR=0.79,95%CI: 0.75-0.83;≥25.0 kg/m2:aOR=0.70,95%CI: 0.66-0.74), abdominal obesity (aOR=0.91, 95%CI: 0.86-0.96), chronic obstructive pulmonary disease (aOR=1.15, 95%CI: 1.09-1.22), cancer (aOR=3.03, 95%CI: 2.84-3.23), heart failure (aOR=1.44, 95%CI: 1.35-1.54) and myocardial infarction (aOR=1.54, 95%CI:1.16-2.04) were independent risk factors of anemia in CKD patients. Among stage 3-5 CKD patients with anemia, 12.03% received iron therapy, and 4.78% received treatment with erythropoiesis-stimulating agent (ESA) within 12 months after anemia was diagnosed. Conclusions: The prevalence of anemia in CKD patients was high in Yinzhou. However, the treatment rate of iron therapy and ESA were low. More attention should be paid to the anemia management and treatment in CKD patients.
3.Rapid identification of chronic kidney disease in electronic health record database using computable phenotype combining a common data model.
Huai-Yu WANG ; Jian DU ; Yu YANG ; Hongbo LIN ; Beiyan BAO ; Guohui DING ; Chao YANG ; Guilan KONG ; Luxia ZHANG
Chinese Medical Journal 2023;136(7):874-876
5.Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF.
Ji-Hong LIU ; Ze-Lin LI ; Yi-Si LIU ; Huai-De CHU ; Neng-Yuan HU ; Ding-Yu WU ; Lang HUANG ; Shu-Ji LI ; Xiao-Wen LI ; Jian-Ming YANG ; Tian-Ming GAO
Neuroscience Bulletin 2020;36(7):705-718
Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.
6. High resolution 3D intraosseous vascular model of the scaphoid bone reconstructed by micro CT
Zhong-Cheng SHEN ; Ding-Yu WANG ; Xuan FANG ; Huai-Cun LIU ; Wei-Guang ZHANG ; Zhong-Cheng SHEN ; Ding-Yu WANG ; Dong JIANG ; Jia-Kuo YU
Acta Anatomica Sinica 2020;51(4):557-560
[Abstract] Objective The purpose of this study is to construct a high-resolution model focusing on the vascular pattern of the scaphoid by using micro CT and to provide anatomical reference for the daily clinical use. Methods The lead-based contrast was perfused from the brachial artery and then the scaphoid bone was harvested. 3D models of the scaphoid bones were constructed by using micro CT to show how arteries distributed in and on the bones. Results The arteries on the surface stretched from the distal radius covered with scaphoid fossa to the radial side of the waist and then head back to the distal ulna along the dorsoradial ridge, formed like a letter “Ⅴ”. The arteries gathered at the inflection point of the letter “Ⅴ” and the dorsal region. The tubercle region was anastomosed extensively with 3 to 5 major intraosseous vessels originated from the extraosseous vessels covering the waist and the tubercle. There are only 1 to 2 major intraosseous vessels entering the bone via a long route from the ulnar side. The vessels running in the scapholunate ligament didn’t spilt into any intraosseous branches. Conclusion The superficial vascularity formes a “Ⅴ”-like pattern. The inflection point of the letter “Ⅴ” and the dorsal region display a dense vascularization and these vessels contributed a lot to the intraosseous vascularity.
7.Mechanism of mTOR Pathway in K562 cell Apoptosis Induced by Homoharringtonine.
Yi-Han DING ; Jing-Jing WU ; Qian WANG ; Zhi-Kui DENG ; Yu-Feng LI
Journal of Experimental Hematology 2018;26(1):105-109
OBJECTIVETo investigate the effect of homoharringtonine (HHT) on proliferation and apoptosis of CML cell line K562 cells and to explore its possible mechanism through mTOR pathway.
METHODSK562 cells were cultured with different concentrations of HHT or in its combination with mTOR inhibitor rapamycin (RAPA) for 24 hours. The cell viability was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry, the expressions of BCL-6, Caspase-3 and mTOR signal pathway related proteins was assayed by Western blot, the expression of BCL-6 mRNA was determined by RT-PCR.
RESULTSThe HHT inhibited proliferation and induced apoptosis of K562 cells in a concentration-dependent manner(r=0.970). With the increasing of HHT concentration, the expression level mTOR signal pathway related proteins increased(r=0.908), while the mRNA and protein expression levels of BCL-6 decreased(r=-0.961, r=-0.981), as compared with the HHT alone, the combination of HHT with RAPA could down-regulate the expression of mTOR signal pathway related protein and caspase-3, and up-regulated expression of BCL-6.
CONCLUSIONHHT induces apoptosis of K562 cells by inhibiting BCL-6 expression through mTOR signal pathway.
8.Introduction trial of medicine mulberry (Morus nigra) in Chongqing.
Qi-Wei ZENG ; Chao ZHANG ; Hong-Yu CHEN ; Tian-Long DING ; Ai-Chun ZHAO ; Zhong-Huai XIANG ; Ning-Jia HE
China Journal of Chinese Materia Medica 2016;41(8):1450-1455
Medicine mulberry (Morus nigra) mainly distributed in southern areas of Xinjiang Uighur Autonomous Region and introduced by grafting, is a unique Morus species, whose plant number is little. As a traditional herbal medicine, medicine mulberry with high levels of secondary metabolites has important values of scientific research and utilization. In order to solve the introduction problems for medicine mulberry, we have established its rapid propagation system through tissue culture since 2011. The shoots of medicine mulberry through tissue culture were transplanted into the field to carry out an introduction experiment. Here, we firstly reported that the growth status and pest and disease occurrence of medicine mulberry in the field of Chongqing and found that the medicine mulberry through tissue culture had well-developed root system, it showed better growth than medicine mulberry by grafting technique, and Pseudodendrothrips moil was a major pest of medicine mulberry. The introduction technique for medicine mulberry established successfully in this study could lay the foundation for large-scale cultivation and high efficiency utilization of medicine mulberry.
9.High-field intraoperative magnetic resonance imaging suite with neuronavigation system: implementation and preliminary experience in the pituitary adenoma operation with transsphenoidal approach.
Xiang-hui MENG ; Bai-nan XU ; Shao-bo WEI ; Tao ZHOU ; Xiao-lei CHEN ; Xin-guang YU ; Ding-biao ZHOU ; Huai-yu TONG ; Jia-shu ZHANG ; Yan ZHAO ; Yuan-Zheng HOU
Chinese Journal of Surgery 2011;49(8):703-706
OBJECTIVESTo review the preliminary clinical experience with high-field-strength intraoperative magnetic resonance imaging (iMRI) suite with neuronavigation system in the pituitary adenoma operation with transsphenoidal approach.
METHODSFrom March 2009 to December 2010, 31 patients [range, 29 - 76 years, mean age (47 ± 11) years]of pituitary adenoma were operated with transsphenoidal approach and intraoperatively with a movable 1.5 T high-field-strength iMRI suite in combination with neuronavigation system. Tumor size was 1.8 - 7.3 cm, mean (3.5 ± 1.2) cm. Twenty-five cases were non-functional pituitary adenoma, 4 cases were prolactin-secreting pituitary adenoma, 2 cases were growth hormone-secreting pituitary adenoma. Thirty patients' resection with transnasal transsphenoidal approach were performed, one patient with transoral transsphenoidal approach was performed.
RESULTSIn 12 cases of 30 patients who planed to totally remove tumor, iMRI had revealed residual lesions and resulted in the change of the surgical strategy, 2 invasive cavernous sinus cases no further resection of the tumor because of internal carotid artery encasement, the other 10 cases resected further, eventually. Finally, 8 cases were totally removed. The ratio of total removal tumor was enhanced to 86.7% (26/30) from 60.0% (18/30). There was no perioperative mortality.
CONCLUSIONSHigh-field-strength iMRI suite with neuronavigation system provides valuable information of tumor resection that allows intraoperative modification of the surgical strategy. It could be very helpful to maximize the resection of the pituitary adenoma and minimize the injury to neurological function.
Adenoma ; surgery ; Adult ; Aged ; Cavernous Sinus ; surgery ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Neuronavigation ; methods ; Pituitary Neoplasms ; surgery
10.Accuracy of mixed venous oxygen saturation in reflecting change in cardiac output during off-pump coronary artery bypass grafting
Li ZHENG ; Yu ZHEN ; Ning MA ; Guannan DING ; Qingyuan HUAI ; Jingdong KE ; Ming TIAN
Chinese Journal of Anesthesiology 2010;30(5):589-591
Objective To assess the accuracy of mixed venous oxygen saturation ( S(-v)O2 ) in reflecting the change in CO during off-pump coronary artery bypass grafting (OPCABG) .Methods Twenty-five NYHA Ⅰ -Ⅲ patients of both sexes, aged 50-75 yr, weighing 55-85 kg, undergoing OPCABG, were studied. Anesthesia was induced with midazolam, fentanyl, etomidate and pipecuronium and maintained with propofol infusion and intermittent iv boluses of fentanyl and pipecuronium supplemented with isoflurane if necessary. The patients were mechanically ventilated (VT 8-10 ml/kg, RR 8-10 bpm, I:E 1:2). PETCO2 was maintained at 35-45 mm Hg.Radial artery was cannulated and pulmonary catheter was placed. CI, S(-v)O2 and Hb were monitored and recorded before skin incision, during anastomosis with left anterior descending artery (LAD), right coronary artery (RCA)and left circumflex coronary artery (LCX), when the chest was closed, when the patients' body position was changed and the heart was manipulated. S(-v)O2 and CI were scaled immediately after the pulmonary artery catheter was placed and before anastomosing LAD. Results The CO change in S(-v)O2 was real-time and accurate in reflecting the body positioning and elevation of hearts. There was no simultaneous significant change in CI.Conclusion The CO change in S(-v)O2 is real-time and accurate in reflecting the body positioning and elevation of hearts during OPCABG.

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