1.The relationship between mRNA level of glucocorticoid receptor α, heat shock protein 90, protein level of macrophage migration inhibitory factor and glucocorticoid resistance in systemic lupus erythematosus
Yanchun GUAN ; Yanmin ZHANG ; Meiyun FANG ; Jingfan GUAN ; Xiangnan SUN ; Jiewen ZHANG
Chinese Journal of Internal Medicine 2015;54(11):922-926
Objective To investigate the mRNA level of glucocorticoid receptor α (GRα) and heat shock protein 90 (HSP90) in peripheral blood mononuclear cells (PBMCs) and the plasma protein level of macrophage migration inhibitory factor (MIF) in patients with systemic lupus erythematosus (SLE) and to analyze their association with glucocorticoid (GC) resistance.Methods One hundred and six patients with SLE and thirty-eight healthy controls were enrolled in this study.Transcription levels of GRα and HSP90 were determined by real-time polymerase chain reaction.Enzyme-linked immunosorbent assay was used to detect the protein level of plasma MIF.The association between these parameters and GC resistance was analyzed by Spearman correlation analysis.The multivariate logistic regression model was used to analyze the risk factors for GC resistance.Results The mRNA level of GRα and HSP90 in GC resistance group was significantly lower than that in GC sensitive group [10.18(3.12,17.20) vs 16.83(12.01,24.18), P =0.001;18.46(14.77,26.45) vs 25.84 (17.97,35.90), P =0.005].MIF protein level in GC resistance group was significantly higher than that in GC sensitive group [(23.21 ±7.98) μg/L vs (18.34 ±6.29)μg/L;P =0.013].The mRNA level of HSP90 in the high MIF group was significantly lower than that in the low MIF group [23.67 (13.84,28.32) vs 26.64 (23.61,47.16);P =0.001], as well as HSP90/GRαratio(P =0.008).Additionally, the plasma protein level of MIF was negatively correlated with HSP90 (r =-0.275, P =0.004) and HSP90/GRα ratio(r =-0.341, P < 0.001).SLE activity index score in GC resistance group was significantly higher than that in GC sensitive group [(12.23 ±2.86) μg./L vs (9.63 ± 3.48) μg/L;P =0.003].Logistic regression model indicated that disease activity was an independent risk factor for GC resistance (OR =17.481, 95% CI 1.747-174.903, P =0.015).Conclusions Our preliminary findings suggest that low mRNA level of GRα and HSP90 and high protein level of MIF are associated with GC resistance.Elevated MIF level in SLE patients may play an important role in the development of GC resistance through down-regulating HSP90 and destabilizing the balance of HSP90/ Grα.Disease activity is the risk factor for GC resistance, which might be the viable evidence of therapy response.
2.Correlation of the levels of interleukin-17 and its receptor with myasthenia gravis
Fen LU ; Xu LI ; Wei LI ; Lingzhi QIN ; Mingming MA ; Xiaojing SUN ; Qianlin ZHANG ; Yong YAO ; Xinliang LIANG ; Jiewen ZHANG
Chinese Journal of Neurology 2016;(2):118-122
Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P <0.01; generalized type patients (9.7 ±1.4) pg/ml, t =2.532, P <0.01).In the patients with glucocorticoid treatment, IL-17 levels began to reduce after 1 week treatment and a statistically significant difference was found when compared to the pre-treatment samples (pre-treatment (8.3 ±1.2) pg/ml, 1 week after treatment (6.3 ±0.7) pg/ml, t=2.052, P<0.05) and healthy controls (t =1.933, P<0.05).One month after the glucocorticoid treatment, the levels of IL-17 decreased to the normal level (1 month after treatment (3.9 ±0.6) pg/ml, t=2.630, P <0.01, compared to the pre-treatment; t =1.395, P >0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.
3.Recent advance in dysfunction of mitochondrial dynamics and pathogenesis of Alzheimer's disease
Chenhao GAO ; Zhengyu SUN ; Jiewen ZHANG
Chinese Journal of Neuromedicine 2019;18(4):337-343
The pathogenesis of Alzheimer's disease (AD) has not been fully elucidated.Mitochondria play critical roles in neuronal function;and damage of hippocampal neurons by dysfunction of mitochondrial dynamics is the major pathological mechanism of AD.Improvement of mitochondrial dynamics imbalance in time should alleviate or reverse damage of hippocampal neurons.After a brief overview of basic mechanisms involved in regulation ofmitochondrial fission,fusion,and transportion,and how mitochondrial dynamics affects AD,this review article focuses on discussing the role of key sites such as Drpl,Mfnl/2,Opal and Miro/Milton in regulating mitochondria dynamics and their effects on
4. Analysis of a family with early onset familial Alzheimer′s disease caused by mutation of amyloid precursor protein gene p.V717I
Huayuan WANG ; Miaomiao YANG ; Ruihua SUN ; Jing ZHAO ; Gai LI ; Yingying SHI ; Yajing SUN ; Limin MA ; Jiewen ZHANG
Chinese Journal of Neurology 2019;52(9):752-757
Objective:
To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family.
Methods:
The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3.
Results:
The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy.
Conclusions
The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.
5.Comprehensive testing system for cardiorespiratory interaction research.
Zhengbo ZHANG ; Buqing WANG ; Weidong WANG ; Jiewen ZHENG ; Hongyun LIU ; Kaiyuan LI ; Congcong SUN ; Guojing WANG
Journal of Biomedical Engineering 2013;30(2):395-402
To investigate the modulation effects of breathing movement on cardiovascular system and to study the physiological coupling relationship between respiration and cardiovascular system, we designed a comprehensive testing system for cardiorespiratory interaction research. This system, comprising three parts, i. e. physiological signal conditioning unit, data acquisition and USB medical isolation unit, and a PC based program, can acquire multiple physiological data such as respiratory flow, rib cage and abdomen movement, electrocardiograph, artery pulse wave, cardiac sounds, skin temperature, and electromyography simultaneously under certain experimental protocols. Furthermore this system can be used in research on short-term cardiovascular variability by paced breathing. Preliminary experiments showed that this system could accurately record rib cage and abdomen movement under very low breathing rate, using respiratory inductive plethysmography to acquire respiration signal in direct-current coupling mode. After calibration, this system can be used to estimate ventilation non-intrusively and correctly. The PC based program can generate audio and visual biofeedback signal, and guide the volunteers to perform a slow and regular breathing. An experiment on healthy volunteers showed that this system was able to guide the volunteers to do slow breathing effectively and simultaneously record multiple physiological data during the experiments. Signal processing techniques were used for off-line data analysis, such as non-invasive ventilation calibration, QRS complex wave detection, and respiratory sinus arrhythmia and pulse wave transit time calculation. The experiment result showed that the modulation effect on RR interval, respiratory sinus arrhythmia (RSA), pulse wave transit time (PWTT) by respiration would get stronger with the going of the slow and regular breathing.
Algorithms
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Artifacts
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Autonomic Nervous System
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physiopathology
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Diagnosis, Computer-Assisted
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methods
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Electrocardiography
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Equipment Design
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Heart
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physiology
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Humans
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Lung
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physiology
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Monitoring, Physiologic
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instrumentation
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methods
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Respiration
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Respiratory Mechanics
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physiology
6.Analysis of a family with early onset familial Alzheimer′s disease caused by mutation of amyloid precursor protein gene p.V717I
Huayuan WANG ; Miaomiao YANG ; Ruihua SUN ; Jing ZHAO ; Gai LI ; Yingying SHI ; Yajing SUN ; Limin MA ; Jiewen ZHANG
Chinese Journal of Neurology 2019;52(9):752-757
Objective To analyze the clinical data of a family with early?onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family. Methods The clinical data of a proband who was clinically diagnosed as early?onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3. Results The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta?amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy. Conclusions The study identified the pathogenic mutation of the beta?amyloid precursor protein gene p. V717I in six patients of a family with early?onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early?onset Alzheimer′s disease in Chinese population.
7.Non-weight-bearing area osteotomy of lateral tibial condyle in treating posterior-lateral condyle fracture of tibial plateau
Yongfeng HUO ; Zhaoyang YIN ; Gang XU ; Guangxue GU ; Leiming LI ; Jiewen YU ; Xiao SUN
Chongqing Medicine 2018;47(7):919-922,925
Objective To explore the clinical curative effects of non-weight-bearing area osteotomy of anterior lateral tibial condyle in treating posterior-lateral condyle fracture of tibial plateau.Methods A retrospective analysis was carried out on 24 cases of posterior-lateral condyle fracture of tibial plateau treated by osteotomy of anterior lateral tibial condyle in this hospital from December 2012 to December 2015,including 15 males and 9 females,aged 26-59 years old with an average age of 42.2 years old.Fracture Schatker classification:type Ⅱ in 16 cases,type Ⅴ in 3 cases and type Ⅵ in 5 cases.All 24 cases adopted surgical treatment via the approach of anterior lateral tibial condyle.During operation,the non-bearing area of lateral tibial condyle was cut to expose and reset the posterior-lateral fractured condyle and fix it with lateral raft steel plate.At the time of last follow-up,the recovery of the knee joint function was evaluated according to the knee scoring system of Hospital for Special Surgery (HSS) in USA.Results Twenty-four patients were postoperatively followed up for 12-24 months,with an average of 13.1 months.The Rasmussen score for the postoperative immediate fracture reduction quality averaged (17.3 ± 0.8)points;there were 19 cases of excellent results and 5 cases of good results,with the excellent and good rate of 100 %.Twenty-four cases had no incision infection,no internal fixation loosening or breakage.The X ray film showed that the fracture got healing,and the average healing time was (13.1 ± 1.1) weeks(12-15 weeks).No surgery related complications including blood vessel and nerve damage occurred;2 cases appeared small area of superficial necrosis at the edge of the posterior incision,which was healed after dressing.At the last follow-up,the HSS knee score was(93.0±6.4) points,excellent in 19 cases,good in 4 cases,and fair in 1 case,with the excellent and good rate of 95.8%.Conclusion For the patients with posterior-lateral condyle fracture of tibial platform,non-weight-bearing area osteotomy approach of lateral tibial condyle allows enough space to directly expose the fracture area and carry out operation;combined with lateral raft locking steel plate fixation is more reliableto fixthe fractured bone,with convenient operation positioning,good postoperative functional recovery,fewer complications,and satisfied curative effects.
8.Clinical characteristics of four patients with primary intraspinal lymphoma
Hong YANG ; Weizhou ZANG ; Mingrong XIA ; Yajing SUN ; Jiewen ZHANG
Chinese Journal of Neurology 2018;51(4):288-293
Objective To analyze clinical characteristics of four cases with primary intraspinal lymphoma to achieve early diagnosis of the disease.Methods Clinical data including the clinical presentation,imaging features and pathological characteristics of four patients diagnosed as primary intraspinal lymphoma confirmed surgically and pathologically from February 2014 to February 2017 in Henan Provincial People's Hospital were analyzed retrospectively,and literatures were reviewed.Results The major clinical manifestations of the primary intraspinal lymphoma were as following:persistent or intermittent waist (back) pain,accompanied with both lower limb weakness,dysfunction of motion,loss or disappearance of sensation,incontinence,followed by an acute progressive neurological function deterioration.The imaging showed a single fusiform shape or irregular lump.The T1 WI signal was equal or slightly lower,and T2WI showed equal or slightly higher signal,and the general signal uniform;The lump showed mild or moderate homogeneous enhancement.The group of four cases were B cell non-Hodgkin lymphoma confirmed by pathological biopsy.Conclusions The clinical and imaging features of primary intraspinal lymphoma are lack of specificity and are easy to be misdiaguosed.The diagnosis is mainly based on pathological biopsy.
9.Fatal familial insomnia preliminarily diagnosed as frontotemporal dementia: a case report and literature review
Yajing SUN ; Mingrong XIA ; Hong YANG ; Weizhou ZANG ; Limin MA ; Shenghui WANG ; Hongju ZHANG ; Jiewen ZHANG
Chinese Journal of Neurology 2018;51(4):294-298
Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.
10.Clinical analysis of 11 cases of autoimmune encephalitis with antibodies against contactin-associated protein-like 2
Jing ZHAO ; Yuanxing ZHANG ; Huiqin LIU ; Gai LI ; Huayuan WANG ; Ruihua SUN ; Yingying SHI ; Miaomiao YANG ; Jiewen ZHANG
Chinese Journal of Neurology 2019;52(7):549-554
Objective To explore the clinical features,auxiliary examinations,therapies and prognoses of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods The clinical data of 11 anti-CASPR2 encephalitis patients who were admited to the People's Hospital of Zhengzhou University from March 2015 to April 2018 were retrospectively analyzed.Results The age of these 11 cases was (35.6± 19.4) years (ranged 20-74 years),and eight cases were females.There were seven cases with limbic encephalitis which included six cases of epilepsy,four cases of memory impairment,two cases of mental and behavioral abnormalities.Four cases had peripheral nerve hyperexcitability.Four cases had neuropathic pain.There were six cases with autonomic dysfunction including five cases of constipation,three cases of tachycardia,two cases of hyperhidrosis,two cases of urinary disorder.Seven cases had sleep disorder.Four cases had weight loss.Two cases showed cerebellar symptoms and two cases had hyponatremia.Magnetic resonance imaging scan of the brain showed abnormal signal in two cases,mainly involved medial temporal lobe and the hippocampus.Six cases underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) examination,and three cases showed abnormalities,including two with temporal hypermetabolism and one with cortical hypermetabolism.Chest enhanced CT and PET-CT showed thymoma in one case.All cases received immunotherapy,and after treatment their symptoms were improved.Long-term follow-up was performed in nine cases,and three cases relapsed.Conclusions The major clinical manifestations of anti-CASPR2 encephalitis were limbic encephalitis,peripheral nerve hyperexcitability,neuropathic pain,autonomic dysfunction,insomnia and so on.Immunotherapy was effective and some patients may have recurrence.