1.Prokaryotic Expression of eBCMA-Fc Fusion Protein, a Soluble BLyS Receptor, with Computer-aided Molecular Design in E. coli
Jian SUN ; Jiannan FENG ; Zhou LIN ; Yan LI ; Beifen SHEN
Chinese Journal of Biochemistry and Molecular Biology 2008;24(2):127-133
B cell maturation antigen (BCMA) is a receptor of B lymphocyte stimulator (BLyS). Human IgG1Fc fusion proteins with the extracellular domain of BCMA(eBCMA), also called decoy receptors, have beenused as a potential BLyS antagonists to block BLyS activities. In order to design novel BLyS antagonistpeptides, computer-aided homologue modeling was used to construct an eBCMA-Fc fusion protein based on thecrystal structures of BCMA and Fc fragmant. To ensure the activity of eBCMA not to be interfered by Fcfusion, the root mean square distance (RMSD) for eBCMA and Fc were calculated to be 0.036 nm and 0.064nm, respectively, based on molecular docking modeling. An eBCMA-Fc fusion gene was constructed andintroduced into E. coli for expression. As expected, the purified 36 kD eBCMA-Fc fusion protein was able tobind BLyS in vitro at a dosage-dependent manner and demonstrated an anti-proliferative activity induced byBLyS in Daudi cells. The results have provided useful information on the evaluation of computer modeling andthe in vitro biological activity for the design of potential BLyS antagonist peptides.
2.The relationship between pillow height and cervical intervertebral disc stress in lateral decubitus position by three-dimensional finite element analysis
Yiqiang ZHOU ; Weishen LIN ; Canhui ZHANG ; Jiannan HONG ; Jianxin ZHANG
International Journal of Biomedical Engineering 2017;40(2):113-117,封3
Objective To analyze the relationship between pillow height and cervical intervertebral disc stress in lateral decubitus position of the human body using three-dimensional finite element method,and to provide the basis for appropriate pillow selection.Methods A cervical spine CT scan was performed on a normal male volunteer.The medical 3D image reconstruction software (Mimics),reverse engineering software (Geomagic Studio) and finite element software (MSC.Patran) were collectively used to establish three-dimensional finite element models of the whole cervical spine under three lateral decubitus conditions,includes pillow height of 10 cm (cervical spine leftward flexion),17 cm (cervical spine neutral),and 25 cm (cervical spine rightward flexion).Moreover,the finite element analysis and calculation of the three models were conducted.Results The Von-Mises stress,maximal principal stress and maximum shear stress of the model in cervical spine neutral (pillow height=17 cm) were all significantly lower than those of the cervical spine lateral model.Conclusions When the cervical coronal plane is in neutral position,the cervical discs can achieve the best stress distribution state.In lateral decubitus position of the human body,a appropriate pillow height should make the cervical vertebrae in neutral position.
3.Evaluation on Medication Route of Puerarin by Plasma Concentration- Time Cur ve and Histodistribution Characteristics in Mice
Yanhong WU ; Ziren SU ; Jiannan CHEN ; Ji LIN ; Xiaoping LAI
Traditional Chinese Drug Research & Clinical Pharmacology 1993;0(02):-
Objective The rational medication route of puerarin was explore d by studying the concentration- time curve and by comparing the histological and organic distribution difference of puerarin administered by intravenous injecti on or gastric gavage in mice, so as to supply a referential data for its rationa l application. Methods The NIH mice were used as experimental subject. The pu erarin concentrations in the plasma, tissue and organs at different time points were determined by HPLC. The PK solutions 2.0 program, a noncompartmental model software, was applied to calculate the pharmacokinetic parameters of puerarin an d to construct its plasma concentration- time curve. Results (1)The pharmacok inetic parameters of puerarin in mice were shown that the T1/2E of puerarin susp ension (0.2 mg? g- 1) by oral administration is 38.061min, CL =991.534 mL? mi n- 1, Cmax =3.6? g? mL- 1, Tmax =30 min, and AUC(0- ∞ ) =201.7? g? min? mL- 1, the bioavailability of puerarin suspension is 3.77 % compared to i.v puerarin injection. (2) Administered by intravenous injection (i.v), the puerari n distributed in the liver, kidney, plasma, spleen, muscle, lung, uterus and tes ticle rapidly, and the concentration of puerarin was the highest in the liver an d kidney and lower in the heart and brain. Distribution of puerarin suspension b y oral administration is similar to puerarin injection by i.v. However, the conc entration of puerarin in the tissues and organs by oral administration was lower than by i.v; the liver/heart, liver/brain, kidney/heart and kidney/brain concen tration ratios of puerarin by gavage administration were lower than those by i.v . Conclusion The bioavailability of puerarin by oral administration was poor, but the histological distribution characteristics of puerarin shows that the tox ic and side effects of puerarin are lesser by oral use than by intravenous injec tion.
4.Applying matching matrix, factor analysis and clustering analysis to investigation of characteristics of syndromes of phlegm and blood stasis in patients with coronary heart disease
Lin LI ; Xiaodong LI ; Jiannan SONG ; Xiangzhong FANG ; Yang MIAO ; Qian LIN
Journal of Integrative Medicine 2006;4(4):343-7
OBJECTIVE: To investigate the characteristics of syndromes of phlegm and blood stasis in patients with coronary heart disease by multiple statistical methods of matching matrix, factor analysis and clustering analysis, and to provide some references for classification and normalization of diagnosis of syndromes of phlegm and blood stasis of coronary heart disease. METHODS: The correlations among 46 kinds of symptoms in syndrome of non-phlegm and non-blood stasis, syndrome of blood stasis, syndrome of phlegm and syndrome of phlegm-blood stasis blocking in 200 patients with coronary heart disease were analyzed by matching matrix, factor analysis and clustering analysis. RESULTS: The manifestations of tongue and pulse in syndromes of phlegm and blood stasis were significantly different from those in syndrome of non-phlegm and non-blood stasis. The pathogenesis of viscera in syndromes of phlegm and blood stasis lied in the heart and kidney, and the syndrome of deficiency of heart qi was the most common one while the syndrome of deficiency of kidney qi took the secondary place. The syndrome of phlegm was often accompanied by syndrome of deficiency of spleen qi. Only 15 ones of 46 clinical symptoms showed high frequency in concomitant appearance in syndrome of blood stasis, syndrome of phlegm and syndrome of phlegm-blood stasis blocking. Apart from having the common symptoms in syndrome of deficiency in origin, the syndrome of phlegm especially showed white and greasy fur and slippery pulse as well as distention and fullness of chest and abdominal distension; the syndrome of blood stasis showed purplish tongue and ecchymosis on tongue as well as fixed pain; and the syndrome of phlegm-blood stasis blocking showed the main symptoms of both syndrome of phlegm and syndrome of blood stasis. CONCLUSION: The statistical methods of matching matrix, factor analysis and clustering analysis are convenient, and can definitely indicate the clinical characteristics and syndrome differentiation of viscera of different syndromes of phlegm and blood stasis, which are beneficial to further research of diagnosis and differentiation of such syndromes of coronary heart disease.
5.Selective application of type Ⅰ and type Ⅱ bundled pancreaticojejunostomy
Qingsong WU ; Yafei LIN ; Jiafeng ZHAO ; Jiannan WANG ; Congyun HUANG ; Xiaolong ZHANG ; Jianhua ZHU
Chinese Journal of Pancreatology 2011;11(1):11-13
Objective To analyze and summarize the efficacy and the experience in the application of type Ⅰ and type Ⅱ bundled pancreaticojejunostomy in pancreaticoduodenectomy. Methods Between Jan.2005 and Dec. 2009, a total of 38 patients who underwent bundled pancreaticojejunostomy was enrolled, and their clinical data were retrospectively analyzed. 20 patients received type Ⅰ bundled pancreaticojejunostomy and 18 patients received type Ⅱ bundled pancreaticojejunostomy. The operative time, postoperative hospital stay, mortality and complications were compared. Results The operative time of type Ⅰ bundled pancreaticojejunostomy was (91 ± 20) min, and it was (63 ± 21) min in type Ⅱ procedure, and the difference was statistically significant (P < 0. 05). The mortality and complications, postoperative hospital stay were 10.0%(2/20), 45.0% (9/20) and (20 ±2)d in type Ⅰ procedure, while they were 5.6% (1/18),38.9% (7/18) and(23 ±2)d in type Ⅱ procedure, and the difference was not statistically significant.Conclusions There was no significant difference in the effects between type Ⅰ and type Ⅱ bundled pancreaticojejunostomy. Carefully selective application of type Ⅰ and type Ⅱ bundled pancreaticojejunostomy helps complete these procedures.
6.Study on relationship between polymorphism of apolipoprotein E gene and syndromes of phlegm and blood stasis in patients with coronary heart disease
Tao OUYANG ; Jiannan SONG ; Yang MIAO ; Qian LIN ; Xiaohong NIU ; Hong JIN ; Bing CHEN
Journal of Integrative Medicine 2005;3(6):438-42
OBJECTIVE: To explore the relationship between polymorphism of apolipoprotein E (ApoE) exon 4 gene and different syndromes in patients with coronary heart disease (CHD). METHODS: Two hundred patients with CHD were divided into four groups according to syndrome differentiation, including syndrome of phlegm (PS), syndrome of blood stasis (BSS), syndrome of phlegm-blood stasis blocking (PBBS) and syndrome of non-phlegm and non-blood stasis (NPNBS). One hundred healthy volunteers were included in control group. Blood lipids were measured by routine examination. Total DNA of peripheral blood was extracted. ApoE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. All data were analyzed by SAS software. RESULTS: (1)The occurrence rate of epsilon4 allele of ApoE in patients with CHD was 19.5%, significantly higher than 9.5% in the control group (P<0.05), and the E 3/4 genotype was especially more frequent (P<0.01). (2) The levels of total cholesterol (TC), total triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in patients with epsilon4 were higher than those in patients without epsilon4 (P<0.01). (3) The frequencies of epsilon4 allele and E3/4 genotype in patients with PS were significantly higher than those in patients with BSS (P<0.05). CONCLUSION: ApoE epsilon4 allele, especially E3/4 genotype, is the risk factor of CHD. There is a relatively close relationship between patients with ApoE epsilon4 allele and PS. It may be one of the main susceptible genes in CHD patients with PS.
7.Surgical and orthodontic management of maxillary palatal impacted canines guided by cone-beam compu-ted tomography
Jiannan YU ; Lin WANG ; Zhendong WANG ; Sheng SHAO ; Yuan LI ; Chunyang ZHAO
Journal of Practical Stomatology 2015;(1):36-40
Objective:To assess the guidance of 3D reconstruction in the surgical and orthodontic management of maxillary palatal impacted canines with cone-beam computed tomography (CBCT).Methods:22 adolescent patients with 26 impacted maxillary conines were examined by CBCT.CBCT 3D reconstruction was used to observe the impaction of the canines.Measurements were taken to evaluate spatial relationship between the canine and adjacent structures and resorption of neighboring incisor roots.Results:CBCT was effective to localize the impacted canines.All of the maxillary palatal impacted canines inclinated mesially,angles of impacted ca-nines to occlusal plane were 61.1°±18.1°,there were 8,5,3 and 10 impacted canines found in classⅠ,Ⅱ,Ⅲ and Ⅳ mesial mal-position respectively.3 adjacent lateral incisors and 2 central incisors were extracted because of severely root resorption.Normal occlu-sion was achieved for 26 impacted canines by the traction of the canines into dental arch and reaching the occlusal plane.Conclusion:CBCT can spatially show the palatal impaction of maxillary canines and the relationship to adjacent tooth,can guide the treatment plan and traction direction,therefore increase therapeutic effect.
8.Clinical features and treatment outcome of four patients with Kallmann syndrome caused by fibroblast growth factor receptor-1 gene mutation
Yue XU ; Bing HAN ; Hui ZHU ; Fangqin XU ; Xuemeng LIU ; Wei LIU ; Jiannan LIN ; Shuangxia ZHAO ; Huaidong SONG ; Jie QIAO
Chinese Journal of Endocrinology and Metabolism 2021;37(5):447-452
Objective:To investigate the clinical features and treatment outcome of Kallmann syndrome(KS) caused by fibroblast growth factor receptor-1(FGFR1) gene mutation in 4 patients.Methods:Targeted next-generation sequencing(NGS) was performed on thirty KS and normosmic idiopathic hypogonadotropic hypogonadism(nIHH) patients. FGFR1 mutation was identified in four KS patients. The clinical data, laboratory and imaging examinations, and treatment outcome were retrospectively analyzed.Results:Four male patients, aging from 11 to 22 years old, presented as micropenis, and with olfactory dysfunction. Among them, two had history of cryptorchidism, three had history of cleft lip and palate repair surgery. The most severe patient presented with short stature, left microtia and dental agenesis. FGFR1 heterozygous mutation was identified in all four patients, two were point mutation(p.Y374X; p. E670K), and the other was frameshift mutation(p.S346Yfs*61; p.S723*fs*1). One patient, who started treatment of the pulsatile GnRH pump during his youth, succeeded in having two babies.Conclusion:Patients with Kallmann syndrome caused by FGFR1 mutation presents complex clinical manifestations. Besides dysosmia, micropenis, microrchidia, and delayed pubertal development are the main clinical manifestations in male patients. Symptoms such as cleft lip and palate are helpful for early recognition. Genotyping analysis is crucial to confirm the diagnosis. The pulsatile GnRH pump can produce satisfactory therapeutic effect, but the age of initiating therapy should be carefully considered.
9.Evaluation and applications of antibody variable stability
Yu CHEN ; Jing YANG ; Xinying LI ; Tingting ZHOU ; Zhou LIN ; Longlong LUO ; Chunxia QIAO ; Ming Lü ; Yan LI ; Beifen SHEN ; Jiannan FENG
Military Medical Sciences 2014;(5):341-346
Objective To study the intrinsic relationships between the binding energy of the antibody light and heavy chains and the conformational characteristics , physical and chemical properties , and to establish a corresponding mathemat-ical model and evaluate the thermal stability of the antibody molecules , which contribute to the antibody design , optimiza-tion and affinity maturation .Methods Based on bioinformatics and computational biology methods , the antibody′s structur-al information with the crystal diffraction data was analyzed .The conformational character of the variable domain of the antibody was studied using distance geometry and computer graphics technology .With the aid of the intermolecular hydrogen bond formation theory and the reaction free energy theory , the dynamic structure and energy characteristics be-tween the heavy and light chain variable regions of the antibody were studied .Furthermore , using nonlinear fitting and regression analysis, a mathematical model was set up .Results According to simulation and statistic analysis , there was a linear relationship between the binding energy and the number of the intermolecular hydrogen bonding , Van der Waals interaction of the heavy and light chains of the antibody .There was polynomial correlation between the binding energy and the physicochemical properties of the antibody .Using the frequency of amino acid position and the established model , the humanized anti-ricin antibody , which could not obtain the stable engineering cell line , was evaluated and optimized .The stable engineering cell line of the humanized anti-ricin antibody was obtained in the experiment .Conclusion The self structure of the antibody variable region ( conformation and physicochemical properties ) has much effect on its stability . The antibody stability can be improved by structural optimization .
10.Hypothalamic-Pituitary-Adrenal Axis and Epilepsy
Xueying BIAN ; Wenxian YANG ; Jiannan LIN ; Biao JIANG ; Xiaoli SHAO
Journal of Clinical Neurology 2024;20(2):131-139
Epilepsy is a recurrent, transient seizure disorder of the nervous system that affects the intellectual development, life and work, and psychological health of patients. People with epilepsy worldwide experience great suffering. Stressful stimuli such as infection, mental stress, and sleep deprivation are important triggers of epilepsy, and chronic stressful stimuli can lead to frequent seizures and comorbidities. The hypothalamic-pituitary-adrenal (HPA) axis is the most important system involved in the body’s stress response, and dysfunction thereof is thought to be associated with core epilepsy symptoms and related psychopathology. This article explores the intrinsic relationships of corticotropin-releasing hormone, adrenocorticotropic hormone, and glucocorticoids with epilepsy in order to reveal the role of the HPA axis in the pathogenesis of epilepsy. We hope that this information will yield future possible directions and ideas for fully understanding the pathogenesis of epilepsy and developing antiepileptic drugs.