1.Downregulation of Neuralized1 in the Hippocampal CA1 Through Reducing CPEB3 Ubiquitination Mediates Synaptic Plasticity Impairment and Cognitive Deficits in Neuropathic Pain.
Yan GAO ; Yiming QIAO ; Xueli WANG ; Manyi ZHU ; Lili YU ; Haozhuang YUAN ; Liren LI ; Nengwei HU ; Ji-Tian XU
Neuroscience Bulletin 2025;41(12):2233-2253
Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals
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Male
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Neuralgia/metabolism*
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Rats
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Down-Regulation/physiology*
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Ubiquitination/physiology*
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Neuronal Plasticity/physiology*
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Rats, Sprague-Dawley
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CA1 Region, Hippocampal/metabolism*
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Cognitive Dysfunction/metabolism*
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RNA-Binding Proteins/metabolism*
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Receptors, AMPA/metabolism*
2.Research progress in clinical diagnosis and treatment of osteosarcoma of the jaw
Manyi LIU ; Long ZHU ; Yang YANG ; Yuelin MA ; Hui FENG
Chinese Journal of Stomatology 2024;59(2):197-203
Osteosarcoma of the jaw (JOS), is a relatively rare type of osteosarcoma, with a unique pathogenesis and pathological manifestations. The clinical manifestation of JOS is not characteristic, and it often needs to be diagnosed by combining radiological and pathological examination. At present, the conventional treatment of JOS is a comprehensive treatment based on surgery and supplemented by radiotherapy and chemotherapy. Recently, the emergence of new therapies such as immunotherapy, gene therapy, phototherapy and traditional Chinese medicine has provided more choices for treatment and brought new hope to patients with JOS. Therefore, this article summarized the current understanding of diagnosis and the latest treatment development of JOS.
3.The evaluation value of MRI dynamic enhancement TIC combined with DWI in benign and malignant breast lesions
Yue WANG ; Manyi HU ; Zibin ZHU
Journal of Chinese Physician 2023;25(6):895-899
Objective:To explore the clinical application value of dynamic contrast-enhanced MRI (DCE) time-signal intensity curve (TIC) combined with diffusion weighted imaging (DWI) in the diagnosis of benign and malignant breast lesions.Methods:This study was a retrospective study. 95 patients with suspected breast cancer who were diagnosed and treated in the Beijing Huairou Hospital from October 2018 to October 2021 were taken as the study subjects. All patients received DCE-TIC and DCE-DWI examinations, and then underwent needle biopsy after imaging examination. We evaluated the diagnostic efficacy of DCE-TIC and DCE-DWI alone and in combination in benign and malignant breast lesions by collecting general clinical data and apparent diffusion coefficient (ADC) values of patients, using pathological examination results as the " gold standard" .Results:A total of 95 patients with suspected breast cancer were diagnosed as benign lesions in 25 cases and malignant lesions in 70 cases after biopsy. Compared with benign lesions, the tumor diameter and ADC value of malignant lesions were significantly different (all P<0.05). The eceiver operating characteristic (ROC) curve of subjects was drawn, and the area under the curve (AUC) of DCE-DWI diagnosis of breast cancer was 0.826. 95 suspected breast cancer patients were diagnosed by DCE-TIC in 28 cases of type Ⅰ, 27 cases of type Ⅱ, and 40 cases of type Ⅲ. With the pathological diagnosis results as the " gold standard", the accuracy, sensitivity, and negative predictive value of DCE-TIC combined with DCE-DWI in the diagnosis of breast cancer were higher than those of a single diagnosis, with a statistically significant difference (all P<0.05); The specificity and positive predictive value of combined diagnosis were not statistically significant compared to single diagnosis (all P>0.05). Conclusions:Both DCE-TIC and DCE-DWI can differentiate benign and malignant breast lesions, and the accuracy, sensitivity, and positive predictive value of combined diagnosis are higher than those of single diagnosis. The combination of DCE-TIC and DCE-DWI can help improve the differential efficiency of breast lesion properties.
4.Modified all-arthroscopic reconstruction of medial patellofemoral ligament for the treatment of recurrent patellar dislocation
Mingjin ZHONG ; Jiaming CUI ; Zirong HUANG ; Yuyin CAI ; Wenzhe FENG ; Kang CHEN ; Kan OUYANG ; Lei YANG ; Daping WANG ; Manyi WANG ; Weimin ZHU
Chinese Journal of Trauma 2023;39(8):695-702
Objective:To evaluate the clinical efficacy of modified all-arthroscopic reconstruction of medial patella femoral ligament (MPFL) for the treatment of recurrent patellar dislocation.Methods:A retrospective case series study was conducted to analyze the clinical data of 38 patients (46 knees) with recurrent patellar dislocation, who were treated at First Affiliated Hospital of Shenzhen University from January 2017 to January 2020. The patients included 12 males (12 knees) and 26 females (34 knees), aged 14-40 years [(24.6±5.4)years]. All patients underwent the modified all-arthroscopic MPFL reconstruction procedure. The femoral tunnel locations were assessed by 3D-CT immediately after surgery. The MRI was performed at 6 and 12 months after operation to assess the healing morphology of the reconstructed MPFL. The Lysholm score and Kujala score were used to assess the knee function before operation, at 6 months after operation, at 12 months after operation and at the last follow-up. The time to return to sports as well as complications were observed.Results:All patients were followed up for 26-48 months [(32.4±8.6)months]. Postoperative 3D-CT examination showed that the femoral tunnels were located in the groove area of the medial epicondyle of the femur and the adductor tubercle. At 6 and 12 months after operation, MRI T2 images showed that the reconstructed MPFL had a low signal and well tensioned ligament tissue, indicating that the MPFL was healed well. The Lysholm scores at 6 and 12 months postoperatively and at the last follow-up were (81.1±12.0)points, (91.2±3.8)points, and (92.2±9.8)points, respectively, being significantly higher than the preoperative (52.4±10.6)points (all P<0.01). The Kujala scores at 6 and 12 months postoperatively and at the last follow-up were (85.4±3.9)points, (91.4±3.6)points, and (93.1±8.5)points, respectively, being significantly higher than the preoperative (55.2±6.8)points (all P<0.01). Compared with 6 months postoperatively, the Lysholm score and Kujala score were significantly improved at 12 months postoperatively and at the last follow-up (all P<0.05). All patients returned to sports, with the time to return to sports for 3-12 months [(8.7±2.3)months] after operation. One patient had poor wound healing but was healed after dressing changes. No wound infection, nerve injury, joint stiffness, patella re-dislocation or other complications occurred. Conclusion:For recurrent patellar dislocation, the modified all-arthroscopic MPFL reconstruction has advantages of accurate bone tunnel positioning, good ligament healing, good function recovery, early return to sports, and less postoperative complications.
5.Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up
Lin WANG ; Jingjing MIAO ; Huageng HUANG ; Boyu CHEN ; Xiao XIAO ; Manyi ZHU ; Yingshan LIANG ; Weiwei XIAO ; Shaomin HUANG ; Yinglin PENG ; Xiaowu DENG ; Xing LV ; Weixiong XIA ; Yanqun XIANG ; Xiang GUO ; Fei HAN ; Chong ZHAO
Cancer Research and Treatment 2022;54(1):118-129
Purpose:
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods:
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results:
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.
6.Reliability and validity of Chinese version of Xerostomia Questionnaire in nasopharyngeal carcinoma patients undergoing radiotherapy
Lin WANG ; Manyi ZHU ; Yuqing HUANG ; Jiawen HUANG ; Boyu CHEN ; Muping DI ; Jingjing MIAO ; Chong ZHAO
Chinese Journal of Radiation Oncology 2019;28(8):566-570
Objective To evaluate the validity and reliability of the Chinese version of Xerostomia Questionnaire ( XQ-C) in nasopharyngeal carcinoma patients treated with radiotherapy. Methods XQ-C was translated according to the International Quality of Life Assessment project approach. Patients with nasopharyngeal carcinoma in different radiotherapy stages were enrolled in this study and assessed by using the XQ-C. The validity and reliability of the questionnaire results were evaluated. The content validity was assessed by experts grading method. The construct validity was assessed by exploratory factor analysis. The discriminant validity was determined by non-parametric method. The reliability was evaluated by Cronbach′s α and split-half reliability to assess the internal consistency. Results A total of 212 questionnaires were completely filled out. Content validity showed that the item content validity index ( I-CVI) ≥0.80, Scale-CVI/Ave=0.97, and P value of Kendall′s W test was 0.701. Exploratory factor analysis revealed that XQ-C was a unidimensional scale. The scale scores of patients at different stages of radiotherapy significantly differed, suggesting that the discriminant validity was good. Cronbach′s α of the scale was 0.951 and Guttman′s semi-reliability coefficient was 0.940. Conclusion The XQ-C is valid and reliable, which can be widely applied in the clinical diagnosis, treatment and research of xerostomia in Chinese nasopharyngeal carcinoma patients after radiotherapy.
7.Clopidogrel and surgical timing for senile hip fractures
Dongchen YAO ; Minghui YANG ; Shiwen ZHU ; Xinbao WU ; Manyi WANG
Chinese Journal of Orthopaedic Trauma 2018;20(7):594-600
Hip fractures,with an increasing morbidity in the elderly patients,pose a serious threat to the health of the aged.At the moment,surgery is the preferred treatment for the vast majority of these patients.Early surgical intervention is strongly recommended by most guidelines and articles.It is still controversial,however,whether surgery should be postponed or performed and whether medication therapy should be withdrawn or continued in some of the elderly patients with hip fracture who are taking anticoagulant or antithrombotic drugs before they are injured.Clopidogrel is one of the anti-platelet drugs commonly used clinically.This article reviews the literature regarding the impact of clopidogrel on surgical timing for hip fractures in the aged,hoping to provide useful clues to the clinical study and practice.
8.Great trochanteric digastric osteotomy and surgical dislocation for treatment of Pipkin Ⅳ fractures
Qiyong CAO ; Bosong ZHANG ; Chunpeng ZHAO ; Shiwen ZHU ; Manyi WANG ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2017;19(8):662-668
Objective To discuss the clinical outcomes of trochanteric digastric osteotomy and surgical hip dislocation for treatment of Pipkin Ⅳ fractures. Methods We retrospectively reviewed the 12 patients with Pipkin Ⅳ fracture who had been treated by trochanteric digastric osteotomy and surgical hip dislocation from February 2012 to June 2016. They were 10 males and 2 females, with an average age of 44. 1 years ( from 24 to 63 years ) . According to the Pipkin classification for femoral head fractures, 9 fractures were type Ⅰand 3 type Ⅱ; according to Letournel-Judet classification for acetabular fractures, 10 were posterior wall fractures ( 9 belonging to the posterior superior subgroup ) and 2 transverse plus posterior wall fractures ( one involving the posterior wall belonging to the posterior superior subgroup ) . The operation time, blood loss, complications and functional results were recorded. Results The operation time averaged 165 min ( from 150 to 195 min ); the blood loss averaged 850 mL ( from 500 to 1, 200 mL ) . A spring plate was used additionally for posterior wall fracture in 7 cases. All the 12 cases obtained an average follow-up of 19 months ( from 6 to 52 months ) . Motion function was fully recovered from 6 weeks to 4 months after operation in 2 cases of preoperative incomplete sciatic nerve injury and in one case of iatrogenic incomplete sciatic nerve injury. Anatomical reduction was achieved in all femoral head fractures. According to the Matta criteria for acetabular fractures, anatomical reduction was achieved in 9 cases, good reduction in 2 and poor reduction in one. Heterotopic ossification occurred in 4 cases ( gradeⅠin one, gradeⅡin 2 and gradeⅢin one by the Brooker grading system ) . The trochanteric osteotomy was repeated in one case. No femoral head avascular necrosis was found. According to the modified Merle d'Aubigné and Postel scoring at the final follow-ups, the functional results of the affected hip were excellent in 4 cases, good in 7 and poor in one. Conclusion Trochanteric digastric osteotomy and surgical hip dislocation is a safe and effective treatment for Pipkin Ⅳ fractures.
9.DTI analysis on white matter changes in children with ametropic amblyopia
Fengming WU ; Yajun LI ; Manyi XIAO ; Xin WEI ; Zhu HAO ; Jin LIU
Recent Advances in Ophthalmology 2017;37(6):551-554,558
Objective To evaluate white matter nerve fiber changes of children with binocular ametropic amblyopia by applying the technology of diffusion tensor imaging and the whole brain analysis method of deterministic tractography,and analyze its correlation with visual acuity.Methods Fourteen binocular ametropic amblyopia children was collected from the Second Xiangya Hospital of Central South University as study subject of experimental group,14 cases of normal sight children as the control group.All children were scanned by MRI system,conventional MRI examination,3DTlWI scan were made,then echo-planar sequence scanning was used to obtain diffusion tensor imaging.Quantitative analysis was made to all diffusion tensor imaging using deterministic tractography.Using the experimental group tracts with statistic changes of FA value,volume and tract count as the region of interest(ROI),the correlation analysis with vision for each ROI was performed.Results Isoametropic amblyopia children demonstrated low FA values in the right ventral and dorsal pathway,right optic radiation and corpus callosum compared to control group.There was low volume of fibers in the bilateral ventral and dorsal pathway,the left optic radiation and body of corpus callosum compared to control group.The tract count of right dorsal pathway had reduced compared to control group.Among FA value,tract count and volume,FA value had the maximum regression coefficient with visual acuity,the regression coefficient of tract count and volume was small.The relative correlation coefficient of FA value at right optic radiation,right ventral pathway and body of corpus callosum with vision acuity were 0.486,0.534 and 0.456,respectively,the right ventral pathway had the maximum correlation with visual acuity.Conclusion Isoametropic amblyopia patients shows abnormal structure on bilateral optic radiation,bilateral ventral and dorsal pathway and body of corpus cailosum,these may cause the capability loss of object recognition and spatial position recognition.The FA value of right ventral pathway has the maximum influence on visual acuity.
10.Management of postoperative infection following open reduction and internal fixation for acetabular fractures
Chunpeng ZHAO ; Qiyong CAO ; Xu SUN ; Yuneng LI ; Minghui YANG ; Honghua WU ; Shiwen ZHU ; Xinbao WU ; Manyi WANG
Chinese Journal of Orthopaedic Trauma 2017;19(11):935-940
Objective To explore the management of postoperative infection following open reduction and internal fixation for acetabular fractures.Methods Ten patients were treated and completely followed up in Beijing Jishuitan Hospital from February 2012 to December 2016 for postoperative infection after open reduction and internal fixation for acetabular fracture.They were 9 males and one female,aged from 14 to 64 years(mean,40.6 years).According to Letournel classification,there were 2 double-column fractures,2 anterior descending transverse fractures,2 anterior column fractures,one posterior wall fracture,and one posterior wall fracture.Eight cases developed surgical regional infection within 2 weeks after internal fixation,and 2 presented with symptoms of infection more than 3 months after fracture fixation.Vacuum sealing drainage (VSD) was used to treat one case of acute superficial infection;open debridement surgery,carrier with sensitive antibiotics and intravenous antibiotics were used to treat 7 cases of acute deep infection and 2 cases of chronic deep infection.Results The infection symptoms disappeared 9 days after removal of VSD device in the one case of acute superficial infection.Normal fracture union was achieved in 6 cases after their infection was controlled;4 cases had to undergo total hip arthroplasty because their articular structure was damaged after control of infection.The 10 patients were followed up for 6 to 54 months (mean,25.7 months).Their Harris scores at the last follow-up averaged 74.8 (from 32 to 92).Conclusions Negative-pressure wound therapy is an effective management for acute superficial infection after acetabular fracture.Deep acute infection needs early repeated debridement combined with sensitive antibiotic carrier to protect joint function.For infection which is difficult to control or chronic infection associated with structural damage,repeated debridement combined with sensitive antibiotic spacer is effective for infection control at the first stage and artificial total hip arthroplasty can be carried out at the second stage when the infection is controlled.

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