1.Establishment of the metabolic syndrome rodent model
Yan GUO ; Xiaoli CHI ; Yuan MA ; Wenxia ZHOU ; Yongxiang ZHANG
Chinese Pharmacological Bulletin 2010;26(4):551-556
AimThe aim of this study was to establish a rodent model with similar characters of human metabolic syndrome(MS).Methods Three species mice and Wistar rats were fed with high energy chows(HEC)for 6 to 23 weeks.Animals were weighted every week.Fasting blood glucose(FBG)together with total cholesterol(TC)and low density lipoprotein-cholesterol(LDL-C)were investigated by oxidase test every two week.And fasting blood insulin(FINS)was determined by radioimmunoassay.Homeostasis model assessment of insulin resistance(HOMA-IR)was calculated as FBG×FINS/22.5.At the end of the experiment,oral glucose tolerance test(OGTT)was performed.Then animals were decapitated,and coel-fat and orchio-fat were collected and weighted to calculate the visceral fat coefficient(VFC).Results FBG,serum TC and LDL-C significantly increased(P<0.01)after 6 weeks feed of HEC in KM mice.The mice also formed abdominal obesity and insulin resistant together with impairment of glucose tolerance(P<0.05 or P<0.01).Though similar to the KM mice,C57BL/6 and BALB/c mice couldn't form abdominal obesity while the latter had increased body weight(P<0.05 or P<0.01).Wistar rats formed hyperlipidemia from 1 to 10 week and hyperglycemia from 10 to 23 week together with insulin resistance and impaired glucose tolerance(P<0.05 or P<0.01).Conclusion KM mice feed with HEC for 6 weeks could successfully establish metabolic syndrome mice model which might be suitable for drug-screening,the major characters includes the formation of abdominal obesity(increase of VFC),the increase of serum TC,LDL-C,FBG and HOMA-IR,and the decrease of OGTT.
2.Efficacy of rituximab in treatment of children with refractory idiopathic thrombocytopenic purpura
Yufang YUAN ; Wenxia KUAI ; Rong HE ; Xiaochun YANG
Chinese Journal of General Practitioners 2012;11(1):67-69
Fifty children with refractory idiopathic thrombocytopenic purpura (RITP) were treated with rituximab (n =26) or vincristine (n =24).The response rate,adverse reaction and recurrence rate in two groups were compared.The CD19 +/CD20 + B cells in peripheral blood were detected by flow cytometry in 26 patients before and after RITP treatment.The response rates of rituximab group was significantly higher than that of vincristine group ( 69.2% vs. 37.5%,x2 =9.74,P < 0.01 ). There was no significant difference in the rate of adverse reaction between two groups ( 11.5% vs.8.3%,x2 =0.62,P > 0.05 ).The recurrence rate of rituximab group ( 22.2% ) was significantly lower than that of vincristine group (55.6%,x2 =7.24,P < 0.05 ).In rituximab group the platelet count after treatment was significantly higher than that before treatment ( t =12.48,P <0.01 ),and the ratio of CD19 +/CD20 + B cells decreased significantly after treatment compare to that before treatment ( t =6.71,P <0.05 ).Rituximab is effective in treatment of refractory idiopathic thrombocytopenic purpura in children,which may be associated with decreased B cells in peripheral bloos.
3.Screening and identification of the mimic peptide of Mycobacterium tuberculosis antigen
Wenxia SUN ; Shishan YUAN ; Yunhong TAN ; Xiaoping ZHANG ; Yanyan YU
Chinese Journal of Microbiology and Immunology 2012;32(1):16-19
ObjectiveTo immunoscreen the mimic peptides of Mycobacterium tuberculosis antigen from phage displayed 12-mer peptide library.MethodsSpecific IgG was purified from sera of patients with TB and used as the target to immunoscreen a phage random peptide library of 12 amino acids.Positive clones which were obtained after three rounds of biopanning were detected by ELISA and sequenced.The diagnostic value of the high frequent positive clones were observed by ELISA.Results After 3 rounds of immunoscreening,the eluted phages were enriched effectively.Six kinds of animo acid sequence were obtained from twelve positive phage clones.Sensitivity of the two high frequent positive clones were 71.4% (A2)and 55.4% (A7) respectively.ConclusionThe antigen-mimic peptide was successfully screened from 12 random phage peptide library and the peptides can be recognized by tuberculosis patients' polyclonal antibodies.
4.MAPK cascade signaling and long-term potentiation
Hui YUAN ; Sheng YANG ; Wenxia ZHOU ; Yongxiang ZHANG
Chinese Pharmacological Bulletin 2003;0(07):-
Long-term potentiation(LTP) of synaptic activity in the hippocampal is the most widely researched model of synaptic plasticity,which is believed to underlie the brain function of learning and memory.Mitogen-activated protein kinases(MAPK) respond to a variety of cellular and extracellular stimuli, such as growth factors,cytokines,extracellular mitogen and stresses.MAPK are involved in complex processes such as in cell differentiation,proliferation and programmed cell death.It has been reported that the upstream regulators and downstream substrats of MAPKs still widely exist in the mature neuron.MAPKs cascade induces phosphorylation of many functional protein including some receptors and kinases that is associated with induction and maintain of the LTP in the neuron,indicating that MAPKs do play a crucial role in the synaptic plasticity.Extracellular signal-regulated kinase(ERK),c-Jun N-terminal kinase(JNK) and p38 activity and its relationship with LTP are reviewed.
5.Reliability and Validity of A Novel Hand-held Dynamometer for Muscles Strength of Lower Extremities
Yanbing JIA ; Hao LIU ; Yuan XIONG ; Chushan WANG ; Wenxia HONG ; Linsen ZHONG ; Zhanwu HUANG ; Shijie ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2017;23(5):572-574
Objective To investigate the reliability and validity of a novel hand-held dynamometer, OE-210, for muscles strength of low-er extremities. Methods From March 1st to August 30th, 2016, 38 young adults were tested the muscle strength of quadriceps and ham-strings with OE-210 dynamometer by 2 rators, and were retested by one of the raters three days later. The isokinetic test was also conducted on all the subjects one day afterwards. The intraclass correlation coefficient (ICC) of OE-210 test results and the Pearson's correlation coeffi-cient between results of OE-210 and isokinetic test were calculated. Results The ICC of test-retest were 0.718 to 0.924, and the ICC of in-ter-rater were 0.784 to 0.870. The correlation between muscle performance measured with 2 tools were significant (P<0.001), that was light to medium on quadriceps (r=0.270-0.413), and strong on hamstrings (r=0.582-0.668). Conclusion OE-210 dynamometer was reliable for muscle strength measurement on quadriceps and hamstrings, and the conditions for valid application need further research.
6.The expression and significance of serum c-met in esophageal squamous cell carcinoma of two different nationalities in Xinjiang
Xingming WANG ; Li GUO ; Zhiqiang ZHANG ; Yuan ZHANG ; Wenxia CHENG ; Hongjiang WANG
Tianjin Medical Journal 2015;(1):64-67,68
Objective To explore the relationship between serum expression of c-met protein and clinic pathological features in esophageal squamous cell carcinoma (ESCC) of Kazakh and Han people. Methods A total of 50 samples of ESCC and its corresponding adjacent tissues of Kazak and Han patients were collected. The expression of c-met protein was detected by immunohistochemistry assay. The serum c-met protein was detected in 40 Kazak and Han ESCC samples and 40 Kazak and Han controls using ELISA method. Results The positive expression rates of c-met protein were higher in Kazak and Han esophageal squamous cell carcinoma patients than those in its corresponding adjacent tissues respectively. And the serum expression rates of c-met protein were higher in Kazak and Han esophageal squamous cell carcinoma patients than those of healthy controls. There were significant differences in the different tumor invasion, lymph node metastasis and TNM stage of esophageal squamous cell carcinoma tissue and serum between groups, in which the infiltrated deep muscle and se?rous breakthrough (T3+T4) were higher than the infiltration of the mucosa and submucosa group (T1+T2), with lymph node metastasis was higher than that without lymph node metastasis, and TNM stage of ⅡB+Ⅲwas higher than that ofⅠ+ⅡA. There was no significant difference in the expression of c-met protein between ethnicity, gender, age and degree of differenti?ation. Conclusion The c-met protein expression is related to the occurrence and development, the invasion, metastasis and TNM stage of ESCC in Kazak and Han nationalities. The high expression of c-met protein in tissue and serum may indicate the invasion and metastasis of esophageal cancer and prompt a late clinical stage.
7.A pedigree with X-linked congenital adrenal dysplasia.
Wenxia YUAN ; Junfen FU ; Li LIANG ; Ke HUANG
Chinese Journal of Medical Genetics 2013;30(1):123-125
Adolescent
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Adrenal Hyperplasia, Congenital
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diagnosis
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genetics
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Adrenal Insufficiency
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Child
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Child, Preschool
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DAX-1 Orphan Nuclear Receptor
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genetics
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Female
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Genetic Diseases, X-Linked
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diagnosis
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genetics
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Humans
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Hypoadrenocorticism, Familial
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Male
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Mutation
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Pedigree
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Phenotype
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Young Adult
8.A new mouse model to study the empathic fear and pain behavior
Tianyao SHI ; Yuan FU ; Fengan LI ; Zhiyong XIAO ; Wenxia ZHOU
Chinese Journal of Pharmacology and Toxicology 2023;37(7):551-551
OBJECTIVE Human beings possess the ability to indirectly acquire the emotions of others.This also known as emotional contagion or empathy,enables us to rapidly perceive the emotions of others.However,an excessive empathy may result in heightened fear and sensitivity to pain.Therefore,the establishment of appropri-ate animal models for analyzing neural mechanisms underlying empathy would contribute to pharmacological research on pain sensitivity caused by psychological sus-ceptibility.METHODS We used the observed fear para-digm for assessing contagion of negative emotions in mice.To minimize the impact of emotional contagion dif-ferences caused by the subject change,we established a bilateral observation area and the two mice were trained to observe fear simultaneously.First,two observer(OB)mice were placed on either side of the observational area.Next,a demonstrator(DM)mouse was introduced into the cylindrical shock cage located at the center of the apparatus.The shock cage is made of transparent organic plastic with air holes and has provided ample space for free movement by the DM mouse.During the shock stage,DM mice were subjected to electric stimulation while the behaviors of OB mice on both sides was observed,including freezing,the side and corner time,social interaction behavior.Additionally,c-Fos staining was utilized to confirm distinct local brain activities.RESULTS In the habituation stage,OB mice on both sides showed more social preference for DM mouse,as evidenced by an increase in duration time in the designat-ed interaction zone.During the shock phase,OB mice observed the DM mouse receiving electric shocks and displayed significantly higher levels of fear contagion;however,their fear behavior was not entirely consistent.Some mice exhibited a significant increase in freezing time,while others demonstrated a significant increase in corner and side exploration time.We utilized Z-normal-ization to evaluate changes in emotionality across vari-ous behaviors and identified mice with distinct susceptibil-ities.Fos-positive neurons exhibited higher expression levels in susceptible OB mice,primarily concentrated within brain regions associated with the ascending path-ways of pain perception,such as thalamus,the anterior insular cortex,and anterior cingulate cortex.CONCLU-SION In this study,we have developed an innovative experimental facility that integrates various behavioral tests to evaluate empathic behavior in mice.Our findings highlight the robustness of emotionality measures obtained from individual mice by combining this experi-mental model with the Z-scoring method,facilitating screening for empathic fear or pain-susceptible mice and will helpful for pharmacological evaluation.
9.Predicting Vertical Ground Reaction Force during Treadmill Running Using Principal Component Analysis and Wavelet Neural Network
Dongmei WANG ; Wenxia GUO ; Shufang YUAN ; Jiahui PAN ; Weiya HAO
Journal of Medical Biomechanics 2022;37(4):E706-E712
Objective To establish the method of predicting the vertical ground reaction force (vGRF) during treadmill running based on principal component analysis and wavelet neural network (PCA-WNN). Methods Nine rearfoot strikers were selected and participated in running experiment on an instrumented treadmill at the speed of 12, 14 and 16 km/h. The kinematics data and vGRF were collected using infrared motion capture system and dynamometer treadmill. A three-layer neural network framework was constructed, in which the activation function of the hidden layers was the Morlet function. Velocities of mass center of the thigh, shank and foot as well as joint angles of the hip, knee and ankle were input into the WNN model. The prediction accuracy of the model was evaluated by the coefficient of multiple correlation (CMC) and error. The consistencies between predicted and measured peak GRF were analyzed by Bland-Altman method. Results The CMC between the predicted and measured GRF at different speeds were all greater than 0.99; the root mean square error (RMSE) between the predicted and measured vGRF was 0.18-0.28 BW; and the normalized root mean square error (NRMSE) was 6.20%-8.42%; the NRMSE between the predicted and measured impact forces and propulsive forces were all smaller than 15%. Bland-Altman results showed that the predicted peak errors of propulsive force at 12 km/h and that of impact force and propulsive force at 14 km/h were within the 95% agreement interval. Conclusions The PCA-WNN model constructed in this study can accurately predict the vGRF during treadmill running. The results provide a new method to obtain kinetic data and perform real-time monitoring on a treadmill, which is of great significance for studying running injuries and rehabilitation treatment.
10.Role of the anterior insular cortex microcircuits in observation fear of mice
Fengan LI ; Yuan FU ; Zhiyong XIAO ; Tianyao SHI ; Wenxia ZHOU
Chinese Journal of Pharmacology and Toxicology 2023;37(7):551-552
OBJECTIVE Fear can be learned indi-rectly,but excessive transmission of fear is essential for the development of mental illness.Previous research has indicated that the anterior insular cortex(AIC)may play a crucial role in the process of fear transmission,and abnormal AIC activity is a possible mechanism under-lying various affective disorders.Inhibitory neurons are crucial for maintaining local microcircuit homeostasis.With the support of novel specific neuroregulatory tech-niques,it is now possible to monitor and regulate differ-ent types of neurons in real-time.Therefore,investigating distinct subtypes of inhibitory neurons in the AIC that are involved in fear contagion may provide valuable insights into potential mechanisms underlying mental disorders.METHODS We established a modified observational fear(OF)model.A demonstrator(DM)mouse was placed in an acrylic cup at the center of the apparatus,and two observer(OB)mice were allowed to explore the DM mouse simultaneously from separate areas on either side.During the OF training,electric foot shocks were administered to the DM mouse and freezing,the side and corner time,and social interaction behavior were scored.Next,we characterized the activity patterns of distinct neuronal subtypes in the AIC using GCaMP-based calcium recording.Finally,we employed a Cre-dependent optogenetic approach to selectively modulate excitatory or inhibitory neurons in the AIC,and investigat-ed empathic fear behavior across different Cre transgenic mouse lines(CK2-Cre,PV-Cre,SOM-Cre,VIP-Cre).RESULTS During the training phase,the OB mice exhib-ited significantly higher levels of fear compared to the control group(which did not observe a traumatic event),as evidenced by increased freezing time,decreased interaction time,and increased corner zone time.Calcium fiber recording results suggested that CK2 neurons are involved in risk prediction,while PV and VIP neurons exert inhibitory control on this behavior.Optogenetic silencing of CK2-positive neurons in the AIC through injection of AAV-DIO-NpHR-mCherry in mice demon-strated a significant reduction in empathic fear.Similarly,activation of PV or VIP inhibitory neurons expressing ChR2-eYFP also resulted in a similar effect.However,activation of SOM neurons led to a significant increase in empathic fear.CONCLUSION Our study demonstrated that VIP and PV neuron activity in the AIC attenuates empathetic fear,while SOM and CK2 neuron activity enhances fear expression.These findings shed light on the distinct contributions of various inhibitory interneu-rons in the AIC to fear contagion,indicating their mutual interaction for maintaining local microcircuit homeostasis that regulates empathetic fear behaviors.