1.Heat shock protein 110 improves the immunological effect of an altered peptide ligand of human papilloma virus type 16 E711-20 peptide
Yunsheng XU ; Rongying OU ; Xueqi ZHANG ; Zhiming LI ; Bingxu LI
Chinese Journal of Dermatology 2012;45(4):266-269
ObjectiveTo investigate the adjuvant effect of heatshock protein 110(HSP110) on the immune responses induced by an altered peptide ligand of human papilloma virus type 16 E711-20 peptide (HPV16E711-20).Methods The complex of HSP110 and an altered peptide ligand of HPV16E711-20 was constructed in vitro.Fifteen 6-week-old C57BL/6 female mice were randonly and equally divided into 3 groups,including complex group,ligand group,and phosphate buffered solution (PBS) group,to receive intraperitoneal immunization with the complex (100 μg),peptide (10 μg),and PBS (100 μl) respectively.Immunization was carried out with an interval of 2 weeks for 2 times.Two weeks after the last immunization,the mice were sacrificed followed by the isolation of splenocytes.MTT assay was performed to evaluate the proliferation activity of splenocytes,intracellular staining for interferon(INF)-γ to detect cytotoxic T lymphocytes (CTLs),standard chromium-51 (51Cr) release assay to estimate the lethal effect of specific CTLs on target cells.Statistical analysis was performed by using t test with SPSS 10.0 software.Differences were considered as statistically significant when the P value was less than 0.05.ResultsA significant increase was observed in the proliferation index ( 1.87 ± 0.122 vs.0.32 ± 0.071,t =4.01,P < 0.01 ) of,and percentage of CD8+IFN-γ+ T lymphocytes(3.9% vs.0.4%,t =3.88,P < 0.01 ) among splenocytes from the complex group compared with the ligand group.At the effector-to-target ratio of 100 ∶ 1,50 ∶ 1,25∶ 1 and 12.5 ∶ 1,the death rate of target cells was 54.7%,72.2%,61.5% and 39.8% respectively after incubation with CTLs from the compleximmunized mice,higher than that from the ligand-immunized mice (35.2%,49.3%,28.1%,17.4%,respectively).ConclusionHSP110 could enhance the immunological effect of the altered peptide ligand of HPV16E711-20,and can serve as an immunological adjuvant.
2.Progress on pharmacokinetic studies of therapeutic monoclonal antibodies
Jianjun GUO ; Lili WANG ; Qi ZHANG ; Aobo ZHANG ; Jing ZHU ; Yongyue ZHAO ; Bingxu ZHANG ; Haizhi BU
Chinese Pharmacological Bulletin 2016;(2):172-176
Monoclonal antibody ( mAb ) represents a class of therapeutics experienced dramatic development over the past 30 years. Because of the tremendous differences in physicochemical and biological properties between mAbs and small molecules, the mAb therapeutics significantly differ from the chemical drugs in pharmacokinetic characteristics and underlying mechanisms. Full understanding of those characteristics and mechanisms may efficiently guide the screening and development of mAb medi-cines, and would well support their safety evaluation and clinical dosage regimen designing. This review is to summarize pharma-cokinetics and underlying mechanisms of mAbs from the aspects of absorption, distribution and elimination, as well as the ap-proaches for prediction of mAb pharmacokinetics in humans.
3.Effect of intraperitoneal injection of thalidomide on pain behaviors in a mouse model of bone cancer pain
Yaguo ZHENG ; Zhengliang MA ; Fengmei MEI ; Rui ZHANG ; Bingxu REN ; Juan ZHANG ; Xiaoping GU
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(11):1005-1007
Objective To investigate the effect of intraperitoneal injection of thalidomide on pain behaviors in a mouse model of bone cancer pain. Methods 36 male C3H/HeJ mice were divided randomly into tumor group (n= 18) and sham group (n= 18) ,six mice from each group were chosen to examine the time course of changes in behavior after tumor cells inoculated to the bone. 2 × 105 osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of mice to induce ongoing bone cancer related pain behaviors. The sham group was inoculated by α-MEM without any cells. On the day before inoculation,the tumor mice were divided randomly into tumor + thalidomide group and tumor + vehicle group. The sham group mice were further divided randomly into sham + thalidomide group and sham + vehicle group. Pain ethology indexes such as paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were observed on 1 d before inoculation and on 3 d ,5 d ,7 d, 10 d, 14 d after inoculation. Results ( 1 ) At day 7 after the operation, compared with sham mice ( 1. 70 ± 0. 33 ) g, PWMT of tumor mice decreased to ( 1.07 ± 0. 30) g (P < 0. 05 ). At day 10, PWTL shortened to ( 12.60 ± 1.69 ) s (P < 0. 05 ) compared with sham mice ( 17.70 ± 1.54 ) s. And the pain behaviors of tumor mice were aggravated along with the development of cancer pain. (2) At day 7 after the operation, compared with tumor + vehicle group ( 1. 07 ± 0.39 ) g, PWMT of tumor + thalidomide group increased to ( 1. 53 ± 0. 39 ) g (P <0.05). At day 10, PWTL extended to ( 16.48 ± 1.13 ) s compared with sham mice ( 12.64 ± 1. 56) s (P <0. 05 ). Conclusion Intraperitoneal injection of thalidomide can efficiently relieve mechanical hyperalgia and thermal hyperalgia in a mouse model of bone cancer pain.
4.A case of keratitis-ichthyosis-deafness syndrome complicated by cutaneous squamous cell carcinoma:mutation analysis of the GJB2 gene and literature review
Zhiming LI ; Jingjing LIU ; Xueqi ZHANG ; Xuan XUAN ; Yi ZHANG ; Xiaohua LIN ; Yunsheng XU ; Bingxu LI
Chinese Journal of Dermatology 2015;(12):864-866
Objective To analyze mutations in the GJB2 gene in a Chinese patient with keratitis-ichthyosis-deafness (KID)syndrome complicated by cutaneous squamous cell carcinoma. Methods Clinical data were collected from a patient with KID syndrome complicated by cutaneous squamous cell carcinoma. Peripheral blood samples were obtained from the patient and her parents, and DNA was extracted from these blood samples. PCR was performed to amplify the exon 2 of the GJB2 gene followed by direct DNA sequencing. Results A mutation (c.148G > A)was identified at position 148 in exon 2 of the GJB2 gene, which caused a codon change from GAC to AAC and resulted in the substitution of aspartate by asparagine at position 50 in the connexin26 (Cx26)protein (p.Asp50Asn). Inaddition,anothermutation(c. 79G > A), which led to the substitution of valine by isoleucine at codon 27 in Cx26 (p.Val27Ile), was found at position 79 in exon 2 of the GJB2 gene. Neither of the two mutations was detected in the patient′s parents. Literature review revealed that 13 cases of KID syndrome complicated by cutaneous squamous cell carcinoma had been reported in abroad, and the mutation c.148G > A was detected in the GJB2 gene in all the 7 cases finally diagnosed by gene sequencing. Conclusion GJB2 gene mutations may be responsible for the clinical phenotype of KID syndrome in this Chinese patient, and the mutation c.148G > A may be related to the development of cutaneous squamous cell carcinoma.
5.Benign familial chronic pemphigus in a family: a clinical survey and mutation analysis of ATP2C1 gene
Xueqi ZHANG ; Xiaohong SHAO ; Jianfeng CAI ; Jingjing LIU ; Zhiming LI ; Xiaohua LIN ; Bingxu LI ; Yunsheng XU
Chinese Journal of Dermatology 2013;(1):47-49
Objective To report a Chinese pedigree with benign familial chronic pemphigus (BFCP),and to screen mutations of ATP2C 1 gene in this family.Methods A 39-year-old male patient with BFCP andhis family members underwent a clinical investigation.Blood samples were collected from all the members in this family and from 50 unrelated healthy controls.Genomic DNA was extracted from the blood samples,and PCR was performed to amplify all the 28 exons and flanking sequences of the ATP2C1 gene followed by DNA direct sequencing.The resulted DNA sequences were compared with the reported sequences of APT2C1 gene in Genbank (Number:NM_014382.2 and NC_000003.9).Results There were 24 family members in the four-generation pedigree,with 8 members affected by BFCP.A single-nucleotide substitution,c(1696C→T),in exon 17 of the ATP2C1 gene was identified in all of the members with BFCP,but not in unaffected third-or second-generation members or unrelated healthy controls.This substitution was also found in 1 out of 4 family members of fourth-generation.Conclusions The nonsense mutation c(1696C→T) in the ATP2C1 gene,is likely to be responsible for BFCP in this Chinese four-generation pedigree.The underage family member of fourth-generation who carried the mutation c(1696C→T) but had no clinical symptoms of BFCP,should be closely followed.
6.Papillon-Lefèvre syndrome: a case report and mutation analysis of the cathepsin C gene
Zhiming LI ; Jingjing LIU ; Haigang ZHU ; Xueqi ZHANG ; Xiaohua LIN ; Bingxu LI ; Yunsheng XU
Chinese Journal of Dermatology 2015;48(11):767-769
Objective To analyze mutations in the cathepsin C (CTSC) gene in a patient with Papillon-Lefèvre syndrome (PLS).Methods Clinical data were collected from a patient with PLS.Two milliliters of venous blood samples were obtained from the patient,his parents and 100 unrelated healthy controls separately.DNA was extracted from these blood samples,and PCR was performed to amplify all the 7 exons of the CTSC gene followed by direct DNA sequencing.Results Two heterozygous mutations were observed in the CTSC gene of the patient.One was a novel mutation c.824C > T at position 824 in the exon 6,which resulted in a substitution of ACC (threonine) by ATC (isoleucine) at codon 275 (p.T275I).The other one was the mutation c.1040A > G at position 1040 in the exon 7,causing the substitution of TAT (tyrosine) by TGT (cysteine) at codon 347 (p.Y347C).His father and mother carried the heterozygous mutation c.824C > T and c.1040A > G respectively.Neither of the two mutations was observed in the 100 healthy controls.Conclusions CTSC mutations are responsible for the clinical phenotype of PLS.Identification of the c.824C > T mutation extends the spectrum of mutations in the CTSC gene and provides a basis for genetic diagnosis of PLS.
7.Application of Comprehensive Function Assessment for Disabled Children in Family Care for Children with Cerebral Palsy
Yuxiu LI ; Jieshan XIE ; Yueming HE ; Zhuoting LIN ; Bingxu JIN ; Xiaolan YAN ; Mengtao ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2017;23(9):1113-1116
Objective To apply the Comprehensive Function Assessment for Disabled Children in family care for children with cerebral palsy. Methods From May, 2014 to May, 2015, 120 cerebral palsy children were equally divided into control group and observation group. The control group accepted routine rehabilitation, and the observation group accepted targeted family rehabilitation program based on the evaluation of Comprehensive Function Assessment for Disabled Children. They were assessed with Comprehensive Function Assessment for Disabled Children before and three months after rehabilitation. Results The scores of cognitive function, language function, exercise abil-ity, self-care movement and social adaptation ability improved in both groups after rehabilitation (t>2.498, P<0.05), and improved more in the observation group than in the control group (t>2.062, P<0.05). Conclusion The application of Comprehensive Function Assessment for Disabled Children may help to plan a targeted rehabilitation nursing program for the nurses and the parents, that benefits the rehabilitation for children with cerebral palsy.
8.The Role of CpG Sequences in the Induction of Anti-dsDNA Antibodies
Zhiming LI ; Shizheng XU ; Xiaohua LIN ; Linlin LIN ; Yong ZHANG ; Bingxu LI
Chinese Journal of Dermatology 2003;0(12):-
Objective To investigate the effect of CpG sequences on t he induction of anti-dsDNA antibodies and the possible mechanism. Methods Usin g a synthetic oligodeoxynucleotide (CpG-ODN) containing CpG as an adjuvant, nati ve calf thymus DNA (nCTDNA) was used as the mimic self antigen to immunize norma l BALB/c mice. About one week after immunization, anti-dsDNA antibodies were tes ted by ELISA using nCTDNA and native Escherichia coli DNA (nECDNA) as test antig ens. Results The levels of anti-dsDNA antibodies and cytokines including IL-6, IL-12, IFN- but the binding abilities were different significantly. Conclusion The CpG motif can promote the product ion of cross-reactive anti-dsDNA antibodies in normal mice.
9.Effects of scalp acupuncture plus acupuncture exercise therapy on walking ability in children with spastic cerebral palsy
Yong ZHAO ; Bingxu JIN ; Wenjian ZHAO ; Jixiang CHENG ; Yinying HUANG ; Jiankun GUO ; Yu HAN ; Chuntao ZHANG ; Jianmei FU ; Fuqing ZHANG
Journal of Acupuncture and Tuina Science 2022;20(3):181-186
Objective: To compare the effect of scalp acupuncture and scalp acupuncture plus acupuncture exercise therapy (AET) on walking ability in children with spastic cerebral palsy (CP). Methods: A total of 60 spastic CP children with gross motor function classification system (GMFCS) grades Ⅰ-Ⅲ were divided into a control group and an observation group by the random number table method, with 30 cases in each group. Both groups were treated with the same conventional rehabilitation and scalp acupuncture therapy for CP. The control group received conventional rehabilitation first and then scalp acupuncture. The observation group received AET, which was to receive the conventional rehabilitation and scalp acupuncture simultaneously. Before and after treatment, the clinical efficacy was evaluated by the modified Ashworth scale (MAS) score, scores of dimensions D and E of the gross motor function measure (GMFM) scale, walking speed, and walking distance. Results: During treatment, there were 2 dropouts in the observation group. After 3 courses of treatment, the MAS scores in both the control group and observation group decreased compared with the same group before treatment (P<0.05), and the scores of dimensions D and E of the GMFM, walking speed, and walking distance were increased (P<0.05); the between-group comparison showed that the MAS score in the observation group was lower than that in the control group (P<0.05), and the scores of dimensions D and E of the GMFM, walking speed, and walking distance in the observation group were higher or longer than those in the control group (P<0.05). Conclusion: W ith the same treatments, scalp acupuncture combined with AET is superior to the conventional scalp acupuncture method in reducing lower-limb muscle tone, improving standing balance ability, and walking stability in children with spastic CP.
10.Effect of Acupoint Application of Fangfeng Baishu San on Immunologic Function in Patients with Cerebral Palsy
Yuxiu LI ; Zhenhuan LIU ; Xiaolan YAN ; Tianfu LIU ; Mengtao ZHANG ; Jieshan XIE ; Bingxu JIN ; Yong ZHANG ; Yerong LI
Shanghai Journal of Acupuncture and Moxibustion 2015;(9):833-835
Objective To investigate the effect of acupoint application of Fangfeng Baishu San on immunologic function in patients with cerebral palsy. Methods Sixty patients with cerebral palsy were randomly allocated to treatment and control groups, 30 cases each. The control group received routine rehabilitation training and the treatment group, application of Fangfeng Baishu San on bilateral points Zusanli, Pishu and Feishu in addition. Serum IgG, IgM, IgA, C3 and C4 were measured in the two groups of patients before and after treatment. Statistical analysis was made. Results There were statistically significant pre-/post-treatment differences in serum IgG, IgM and IgA in the treatment group (P<0.05). There were statistically significant post-treatment differences in serum IgG, IgM and IgA between the treatment and control groups (P<0.01). There were no statistically significant post-treatment differences in serum IgG, IgM, IgA, C3 and C4 between the patients with different ages, sexes or CP types (P>0.05). Conclusion Acupoint application of Fangfeng Baishu San can improve immunologic function in patients with cerebral palsy.