1.Effect of electroacupuncture on learning and memory abilities in vascular dementia rats via the NCOA4/FTH1 signaling pathway-mediated ferritinophagy.
Wei SUN ; Yinghua CHEN ; Tong WU ; Hongxu ZHAO ; Haoyu WANG ; Ruiqi QIN ; Xiaoqing SU ; Junfeng LI ; Yuanyu SONG ; Yue MIAO ; Xinran LI ; Yusheng HAN
Chinese Acupuncture & Moxibustion 2025;45(9):1271-1280
OBJECTIVE:
To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD.
METHODS:
A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot.
RESULTS:
Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01).
CONCLUSION
Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals
;
Electroacupuncture
;
Dementia, Vascular/genetics*
;
Male
;
Rats
;
Signal Transduction
;
Humans
;
Memory
;
Rats, Sprague-Dawley
;
Nuclear Receptor Coactivators/genetics*
;
Ferritins/genetics*
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Learning
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Hippocampus/metabolism*
;
Acupuncture Points
2.Research Progress on Immunosenescence in Elderly Patients with Advanced Non-small Cell Lung Cancer and Its Immunotherapy.
Na WANG ; Yaning LUO ; Haoyu LU ; Siyuan CUI ; Kui ZHAO ; Fanming KONG
Chinese Journal of Lung Cancer 2025;28(7):542-550
Lung cancer remains the leading cause of cancer-related incidence and mortality worldwide. Among its histological subtypes, non-small cell lung cancer (NSCLC) accounts for the majority of cases, representing the predominant pathological type. Notably, in the elderly population, NSCLC continues to be a major contributor to cancer-related deaths. With the global ageing population, immunosenescence has emerged as a key factor influencing the occurrence, progression, and the efficacy of immunotherapy of NSCLC. Immunosenescence refers to the age-related decline in immune system function, which manifests as alterations in both the quantity and functionality of immune cells. These include thymic involution, T cell exhaustion, epigenetic modifications, weakened immune responses, and a chronic low-grade inflammatory state. This review comprehensively analyzes the role of immunosenescence in elderly patients with advanced NSCLC and proposes potential therapeutic strategies to intervene in the immunosenescence process. By targeting immunosenescence, these strategies aim to inhibit the progression of NSCLC and improve the effectiveness of immunotherapy.
.
Humans
;
Carcinoma, Non-Small-Cell Lung/genetics*
;
Immunotherapy
;
Lung Neoplasms/genetics*
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Immunosenescence
;
Aged
3.Differences and mechanisms of reproductive damage in male rats caused by single and combined exposures to S-band and X-band microwaves
Yanyang LI ; Yueyue PANG ; Li ZHAO ; Haoyu WANG ; Junqi MEN ; Binwei YAO ; Ruiyun PENG
Military Medical Sciences 2024;48(8):565-571
Objective To study the differences and mechanisms of damage to the reproductive organs of male rats by single and compound exposure to microwaves at 2.856 and 9.375 GHz.Methods A total of 40 male Wistar rats were randomly divided into sham group,S10 group,X10 group and SX5 group.Microwavesat 2.856 and 9.375 GHz were used to expose the rats for 6 min in the S10 and X10 groups with an average power density of 10 mW/cm2,respectively.The SX5 group was sequentiallyexposed to 2.856 and 9.375 GHz microwaves with an average power density of 5 mW/cm2 for 6 min.At 1 and 7 d after exposure,the sperm viability and serum sex hormones were detected by light microscopy and electron microscopy,and testicular tissue structure and oxidative stress and energy metabolism levels were examined.Results The sperm viability,testosterone(T),follicle stimulating hormone(FSH),and inhibin B(INHB)decreased in the S10 and X10 groups at 1 and 7 d after exposure(P<0.01),and in the SX5 group at 7 d after exposure(P<0.05).The LH decreased in all the exposure groups at 1 d after exposure(P<0.01),and increased in the S10 and X10 groups at 7 d after exposure(P<0.05).The spermatogenic epithelium of testicular tissue was lax,spermatogenic cells were edematous and vacuolated,chromatin condensed and shifted side by side,and the damage was significant in the S10 and X10 groups as compared with the SX5 group.The superoxide dismutase(SOD)activity in testis tissue decreased and malondialdehyde(MDA)content increased at 1 and 7 d after exposure in the S10 group(P<0.01).In the X10 group,the SOD decreased at 1 d after exposure(P<0.01).The lactate dehydrogenase(LDH)and succinate dehydrogenase(SDH)activity and adenosine triphosphate(ATP)content in testis tissue decreased at 1 and 7 d after exposure in the S10 and X10 groups(P<0.05).In the SX5 group,the LDH and SDH decreased at 1 d after exposure(P<0.05).Conclusion Single and combined exposure to S-band and X-band microwaves can cause damage to male reproductive organs.The S-band causes damage more significantly than that of X-band.Single-frequency microwave high-intensity exposure causes damage more significantly than that of multi-frequency microwave prolonged combined exposure.The damage is closely related to oxidative stress and energy metabolism.
4.Morphological characteristics analysis for deposition sequencing of overlapping bloodstain patterns
Zunlei QIAN ; Lindi ZHANG ; Mengqi WU ; Haoyu WANG ; Zhao LIU ; Zhenjun JIA
Chinese Journal of Forensic Medicine 2024;39(3):299-303
Objective To explore the morphological characteristics of overlapping bloodstains and judge the deposition sequence of bloodstain patterns.Methods The overlapping bloodstains formed by drip stains and bloody shoe prints were simulated on ceramic tiles,and the morphological characteristic differences of 6 group overlapping bloodstain patterns were analyzed to screen effective indicative characteristics.A survey was held to measure the accuracy of the participants in judging the blood deposition sequence without and with information about the morphological characteristic guidance.Results After participants mastered morphological characteristics,the accuracy of judging deposition sequence increased from 59.5%to 89.0%,and the accuracy of judging dry and wet conditions of the primary bloodstains increased from 45.6%to 65.3%.Conclusion According to the morphological characteristics of bloodstains,not only the deposition sequence of bloodstains can be effectively judged,but also the dry and wet conditions of bloodstains can be judged,so as to infer the time interval of bloodstains deposition,which can provide technical support for the analysis and reconstruction of crime scene.
5.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
6.Analysis of curative effect of V-shape bichannel endoscopy(VBE)system assisted lumbar interbody fu-sion in the treatment of single level lumbar spine diseases
Yunshan FAN ; Haoyu GONG ; Yingchuan ZHAO
Chinese Journal of Spine and Spinal Cord 2024;34(4):380-388
Objectives:To report a V-shape bichannel endoscopy(VBE)system and evaluate the preliminary clinical effects of VBE assisted transforaminal lumbar interbody fusion(VBE-TLIF).Methods:20 patients with lumbar diseases underwent VBE-TLIF surgery in our hospital from January 2020 to April 2021 were retrospectively reviewed.There were 13 males and 7 females,with a mean age of 57.0±11.7 years old(28-77 years old).The operative time and complications were collected,and visual analogue scale(VAS)scores,Oswestry disability index(ODI)before surgery and at 3d,3,6,12 and 18 months after surgery were recorded to evaluate the relief of patients'symptoms.And also,modified MacNab's criteria and radiological examination results at final follow-up were analyzed to to evaluate the overall satisfactory and fusion rate.Results:The average follow-up time of 20 patients was 27.0±3.6 months(22-36 months),and the clinical symptoms of patients relieved significantly.The average VAS leg pain score and VAS back pain score reduced respectively from 6.3±1.6 and 5.7±1.1 before operation to 1.9±0.9 and 2.3±0.8 at 3d postoperatively,and further to 0.7± 0.6 and 0.9±0.7 at 18 months after the surgery,and both with significant differences(P<0.05).Comparing with the preoperative average ODI[(60.2±15.3)%],the ODI at the 18th month after surgery was(15.0±5.8)%,and the difference was with statistical significance(P<0.05).There was one patient experienced transient hip flexion weakness and improved after one month of symptomatic treatment;One patient experienced cage immigration causing nerve root irritation and underwent reoperation,the fusion rate was 95%(19/20);No serious operation related complications occurred.The overall excellent and good rate was 95%by modified MacNab's criteria.Conclusions:VBE-TLIF is a safe and effective minimally invasive lumbar fusion technique,and its primary clinical application is satisfactory in outcomes.
7.The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review
Haoyu WANG ; Chunxia ZHAO ; Qingqing RONG ; Jinghe CAO ; Hongyi CHEN ; Ruolin LI ; Bin ZHANG ; Peng XU
International Journal of Stem Cells 2024;17(3):236-252
Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.
8.Exploration of electroacupuncture at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) for attenuating learning and memory impairment in vascular dementia rats based on NMDAR/CREB/BDNF signaling pathway.
Yuanyu SONG ; Yinghua CHEN ; Wei SUN ; Changqing LI ; Junfeng LI ; Haoyu WANG ; Ruiqi QIN ; Xiaoqing SU ; Tong WU ; Hongxu ZHAO ; Yusheng HAN
Chinese Acupuncture & Moxibustion 2024;44(12):1409-1417
OBJECTIVE:
To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload.
METHODS:
Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca2+-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method.
RESULTS:
Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca2+-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca2+-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05).
CONCLUSION
EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture
;
Male
;
Animals
;
Rats, Sprague-Dawley
;
Learning
;
Memory
;
Signal Transduction
;
Cyclic AMP Response Element-Binding Protein/metabolism*
;
Memory Disorders/therapy*
;
Brain-Derived Neurotrophic Factor/metabolism*
;
Receptors, N-Methyl-D-Aspartate/metabolism*
;
Dementia, Vascular/therapy*
9.Risk factors of gastrointestinal polypectomy concurrent with bleeding in patients with liver cirrhosis
Hao CUI ; Tao HAN ; Baiguo XU ; Haoyu WANG ; Zhengang ZHAO ; Yan LI
Chinese Journal of Hepatology 2023;31(2):147-154
Objective:To investigate and analyze the occurrence and the related risk factors of gastrointestinal polypectomy accompanied by bleeding in patients with liver cirrhosis.Methods:127 cases of gastrointestinal polyps with cirrhosis who had endoscopy at the Endoscopic Center of Tianjin Third Central Hospital between November 2017 and November 2020 were collected. At the same time, 127 cases of gastrointestinal polyps with non-cirrhosis that were treated by endoscopy were collected for comparison. The occurrence of hemorrhagic complications between the two groups was compared. The effects of age, sex, liver function, peripheral blood leukocytes, hemoglobin, platelets, blood glucose, the international normalized ratio (INR), polyp resection method, polyp location, size, number, endoscopic morphology, pathology, the presence or absence of diabetes, portal vein thrombosis, and esophageal varices on polypectomy bleeding in the cirrhosis group were analyzed. The measurement data between groups were compared using the t-test and rank sum test. The χ2 test or Fisher’s exact probability method, and multivariate logistic regression analysis were used for the comparison of categorical data between groups. Results:The number of polypectomy bleeding cases in the cirrhotic group was 21, with a bleeding rate of 16.5%. The number of bleeding cases in the non-cirrhotic group was 3, with a bleeding rate of 2.4%. The bleeding rate was higher in the cirrhosis group when polypectomy was performed ( χ2 = 14.909, P < 0.001). A univariate analysis of the risk factors for gastrointestinal polypectomy associated with bleeding in patients with liver cirrhosis showed that liver function grading, platelets, INR, hemoglobin, degree of esophageal and gastric varices, and the location, shape, size, and pathology of the polyps had a statistically significant impact on bleeding ( P < 0.05). Multivariate logistic regression analysis showed that liver function grade, degree of varicose veins, and polyp location were independent risk factors for bleeding. Patients with Child-Pugh B or C grade liver function were more likely to bleed than those with Child-Pugh A grade ( OR = 4.102, 95% CI 1.133 ~ 14.856), gastric polyps were more likely to bleed than colorectal polyps ( OR = 27.763, 95% CI 5.567 ~ 138.460), and severe esophagogastric varices were more likely to bleed than no varices or mild to moderate varices ( OR = 7.183, 95% CI 1.384 ~ 37.275). Conclusion:Cirrhotic population has higher risk of bleeding during endoscopic gastrointestinal polypectomy than the non-cirrhotic population. Cirrhotic patients with Child-Pugh grades B or C liver function, polyps located in the stomach, severe esophagogastric varices, and other high-risk factors should be listed as a relative contraindication for endoscopic polypectomy.
10.Diffusion Tensor Imaging in the White Matter Changes of Patients with Pituitary Macroadenoma
Haoyu WANG ; Qian HE ; Bo ZHAO ; Shizhen HE ; Chen LIU ; Peng WANG
Journal of Kunming Medical University 2023;44(12):72-78
Objective To investigate the microstructural changes in white matter of pituitary adenoma patients when the anterior visual pathway is compressed using diffusion tensor imaging(DTI)and discuss the clinical significance of these changes.Methods Clinical and MRI data of 25 patients with pituitary adenomas and 25 matched healthy controls were prospectively included.Tract-based spatial statistics(TBSS)was carried out to investigate difference in white matter integrity between 2 groups,which was measured using fractional anisotropy(FA).A correlation between visual function evaluation index and regional FA value was examined using correlation analysis.Results The FA values of bilateral optic radiations and inferior fronto-occipital fasciculus were significantly lower in the research group.The FA values of left optic radiation and inferior fronto-occipital fasciculus were positively correlated to mean deviation and visual field index,negatively correlated to patten standard deviation.The FA values of bilateral optic radiations and inferior fronto-occipital fasciculus were negatively correlated with Bulbo-pontine height.Conclusion Patients with pituitary adenoma may experience damage to the bilateral optic radiation and inferior fronto-occipital fasciculus after compression of the anterior visual pathway,which may affect the patient's visual function,further indicating that DTI can quantitatively assess the microstructure damage of the visual pathway in patients with pituitary adenoma.

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