2.Effects of polysorbates on stability of monoclonal antibody drugs
ZHU Sheng-ying ; CAO Jia-wei ; XU Jin ; CHEN Chen-hui ; GUO Qing-cheng ; LI Jun ; ZHANG Da-peng ; QIAN Wei-zhu ; HOU Sheng ; GUO Huai-zu
Chinese Journal of Biologicals 2023;36(2):172-177
Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.
3.The relationship between HBV genotypes and the efficacy of antiviral therapies in hepatitis B e antigen- positive patients.
Huai-bin ZOU ; Li-min ZHU ; Gui-ming ZHAO ; Shu-ren LIANG ; Jia LI ; Cheng-zhen LU ; Hai LI
Chinese Journal of Hepatology 2007;15(6):425-427
OBJECTIVESTo study the relationship between HBV genotypes and the efficacy of antiviral therapies.
METHODSHBV genotypes of 90 hepatitis B e antigen positive patients with chronic hepatitis B (CHB) were determined by PCR sandwich hybridization-ELISA technique. Forty-one patients with CHB were treated with lamivudine (100 mg/day) for 48 weeks and 49 patients with CHB were given alpha-interferon (3 MU/QOD) therapy for 48 weeks. The serological, biochemical and virological symbols were measured before, during and after treatment for all the patients.
RESULTSOf the 90 patients, genotype B HBV was found in 16 and C in 74. There was no difference in the rate of response to lamivudine treatment between patients with genotype B or C HBV (33.3% vs. 20.0%) after 48 weeks treatment with lamivudine in the 41 patients. Of the 49 HBeAg positive CHB patients treated with alpha-interferon for 48 weeks, in HBV genotype B and C patients the rates of normalization of ALT were 60.0% and 20.5%; the rate of HBeAg turning to negativity was 50.0% and 17.9%; and the rate of HBV DNA undetectability was 50.0% and 17.9%. The rate of response to the interferon treatment was significantly higher in patients with HBV genotype B compared to those with genotype C.
CONCLUSIONSOur study shows that there is no influence on the lamivudine treatment effects for the HBV genotype B and C CHB patients, but the alpha-interferon treatment for HBV genotype B CHB patients is more effective than that for the genotype C ones.
Adolescent ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; Female ; Genome, Viral ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Young Adult
4.Background chloride currents in fetal human nasopharyngeal epithelial cells.
Xue-Rong SUN ; Li-Wei WANG ; Jian-Wen MAO ; Lin-Yan ZHU ; Si-Huai NIE ; Ping ZHONG ; Li-Xin CHEN
Acta Physiologica Sinica 2005;57(3):349-354
To characterize the background current in fetal human nasopharyngeal epithelial cells and clarify its relationship with volume activated Cl(-) currents (I(Cl,vol)), whole-cell patch clamp and cell imaging techniques were employed. Under isotonic conditions, a background current [(5.9+/-2.1) pA/pF at +80 mV, n=21] was detected. The current presented a weak outward rectification and a negligible time-dependent inactivation. The current-voltage relationship showed that the reversal potential of the background current [(-0.73+/-1.7) mV, n=21] was close to the calculated equilibrium potential for Cl(-)(-0.9 mV). Application of extracellular hypertonic stimulation (440 mOsmol/L) suppressed the current by (59.6+/-7.1)% and the inhibition was reversible after returned to isotonic conditions. Bathing the cells in hypotonic solution (160 mOsmol/L) induced a volume-sensitive Cl(-) current. The Cl(-) channel blockers, tamoxifen (20 micromol/L) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (100 micromol/L), inhibited the background current by (74.0+/-5.2)% (P<0.01, n=5) and (60.9+/-8.9)% (P<0.01, n=6) at +80 mV and increased basal cell volume by (107.7+/-2.9)% (P<0.01, n=25) and (104.4+/-2.4)% (P<0.01, n=19), respectively. The data indicate that Cl(-) current is an important component of the background current in fetal human nasopharyngeal epithelial cells. The background Cl(-) current is involved in volume activated Cl(-) current and basal cell volume regulation.
Cells, Cultured
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Chloride Channels
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antagonists & inhibitors
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physiology
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Electrophysiology
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Epithelial Cells
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cytology
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metabolism
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physiology
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Fetus
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Humans
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Nasopharynx
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cytology
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Nitrobenzoates
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pharmacology
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Patch-Clamp Techniques
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Tamoxifen
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pharmacology
5.Detection of chromosome 8 anomalies in ovarian carcinoma by fluorescence in situ hybridization.
Yue-lan DONG ; Chun-hua LI ; Li-xin CHEN ; Huai-ying FENG ; Bao-sheng ZHU
Chinese Journal of Medical Genetics 2003;20(1):59-60
OBJECTIVETo detect the relationship between chromosomal anomalies and the pathogenesis, development and prognosis of ovarian carcinoma.
METHODSThirty-six specimens of ovarian carcinoma (n=12), ovarian benign tumor (n=12), and normal ovary (n=12) were examined by fluorescence in situ hybridization (FISH).
RESULTSTwelve cases of mutations, including trisomy 8, monosomy 8 or tetraploid 8 chromosomal anomalies, were found in the group of ovarian carcinoma, making up 100% (12/12). Three cases of trisomy 8 chromosomal anomalies were found in the group of ovarian benign tumor, accounting for 25% (3/12). No anomaly was found in the normal group. There were significant differences between the three groups, P<0.001.
CONCLUSIONThe above anomalies of chromosome 8 are significantly associated with the pathogenesis and development of ovarian carcinoma. The anomalies may occur in the early stage of the carcinoma, and may be significantly associated with the pathological differentiation and clinical stage of the case.
Adolescent ; Adult ; Aged ; Aneuploidy ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Middle Aged ; Monosomy ; Ovarian Neoplasms ; genetics ; Trisomy
6.Ten-year changes in pathogen, antimicrobial susceptibility and clinical feature of children with bacterial meningitis.
Hong LI ; Yu-Qin ZHANG ; Jin-Ting ZHANG ; Jin ZHU ; Xiao-Jun LIU ; Huai-Li WANG ; Lu-Mei YE
Chinese Journal of Pediatrics 2009;47(4):272-275
OBJECTIVEDespite progress in antibiotic therapy and intensive care, childhood bacterial meningitis (BM) remains a devastating disease. We conducted this study to investigate the changes in clinical characteristics, the etiologic agents and antimicrobial susceptibility of BM during the past 10 years in children under 14 years of age.
METHODSThese 126 patients were divided into two groups according to their date of admission. Group 1 included 64 patients admitted from January 1998 to December 2002, and group 2 included 62 cases admitted from January 2003 to December 2007. All pediatric medical charts of them were reviewed.
RESULTSThe predominant isolated bacteria from CSF were coagulase-negative staphylococcus (17/62, 27.4%) and Escherichia coli (9/62, 14.5%) in group 2. The resistance rate of staphylococcus against oxacillin (MRS) was 68.4% (13/19) in group 2, significantly higher than that of group 1 (16.7%, 2/12). Among 126 cases, 42 had seizure attack and 16 had consciousness disturbance, the proportions of them in group 2 (11/62, 17.7%; 4/62, 6.4%) were lower than those in group 1 (31/64, 48.4%; 12/64, 18.8%, P < 0.05). Cases in group 2 survived with complications [13/62 (21.0%)] and sequelae [11/62 (17.7%)] were lower than those in group 1 (24/64, 37.5%, 23/64, 35.9%, P < 0.05), but the rate of empirical therapy modification in group 2 (21/62, 33.9%) was higher than that in group 1 (7/64, 10.9%, P < 0.01).
CONCLUSIONThe predominant bacteria in children with BM are staphylococcus and Escherichia coli in recent years. The antibiotic resistance rate of bacteria has been higher year after year. The clinical patterns of pediatric BM have changed with a decrease in clinically serious cases, complications and sequelae, but an increase in modification of empirical therapy.
Anti-Bacterial Agents ; pharmacology ; Child ; Child, Preschool ; Cross Infection ; microbiology ; Drug Resistance, Bacterial ; Escherichia coli ; drug effects ; isolation & purification ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial ; epidemiology ; microbiology ; Retrospective Studies ; Staphylococcus epidermidis ; drug effects ; isolation & purification
7.A clinical report of 58 cases of split liver transplantation
Zhijun ZHU ; Wei GAO ; Chong DONG ; Lin WEI ; Tao YANG ; Zhongyang SHEN ; Liying SUN ; Wentao JIANG ; Jianjun ZHANG ; Mingsheng HUAI ; Yamin ZHANG ; Junjie LI ; Cheng PAN
Chinese Journal of Organ Transplantation 2012;33(4):195-199
Objective To summarize the clinical experience in 58 cases of split liver transplantation (SLT).Methods A retrospective analysis was conducted on 58 cases of SLT during June 2006 to January 2011.There were 13 cases performed at the first phase (2006.6-2008.12),and 45 cases at the second phase (2009.1 2011.1). The survival rate of patients,recovery of liver function,re-transplantation rate,incidence of vascular complications and biliary complications were observed,and the causes of death were analyzed.Results The median follow-up time of all the patients was 11.4 months (0-48 months).The 1- and 2-year cumulative survival rate was 77.4% and 68.3% respectively,re-transplantation rate was 6.9%,the incidence of vessel complications was 13.8%,and biliary complication rate was 32.1%.Fifteen cases died,including 8 deaths which were related to surgical complications.Conclusion With the donor split technology improvements and refinements in partial liver transplantation, the survival rate of SLT recipients is significantly increased,but selection of recipients is still the key factor that impacts survival rate of recipients receiving SLT.SLT can expand the resource of liver donors,and adequate selection of recipients can obtain better results.
9. Predictive factors of mortality in extremely preterm infants
Li LIN ; Mingchu FANG ; Huai JIANG ; Minli ZHU ; Shangqin CHEN ; Zhenlang LIN
Chinese Journal of Pediatrics 2018;56(4):274-278
Objective:
To investigate the predictive factors of mortality in extremely preterm infants.
Methods:
The retrospective case-control study was accomplished in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. A total of 268 extremely preterm infants seen from January 1, 1999 to December 31, 2015 were divided into survival group (192 cases) and death group (76 cases). The potential predictive factors of mortality were identified by univariate analysis, and then analyzed by multivariate unconditional Logistic regression analysis. The mortality and predictive factors were also compared between two time periods, which were January 1, 1999 to December 31, 2007 (65 cases) and January 1, 2008 to December 31, 2015 (203 cases).
Results:
The median gestational age (GA) of extremely preterm infants was 27 weeks (23+3-27+6 weeks). The mortality was higher in infants with GA of 25-<26 weeks (
10.Prevalence of uncorrected refractive errors of rural population aged ≥ 50 years in Funing county, Jiangsu province
Mei YANG ; Jing ZHOU ; Fang Jun ZHANG ; Rong Rong ZHU ; Bai QIN ; Hua Li KANG ; Jin Huai GUAN
Recent Advances in Ophthalmology 2017;37(11):1044-1048
Objective To investigate the prevalence of uncorrected refractive errors among urban population aged 50 years and above in Ftming county,Jiangsu province.Methods Survey research was conducted and randomly cluster sampling was used to select individuals aged ≥50 years for visual acuity test and eye examination in Funing county,Jiangsu province.The criteria of uncorrected refractive errors in this study was defined as an improvement of at least 0.2 log MAR (equivalent to 2 lines) in the best corrected visual acuity with the base vision < 0.5 log MAR in daily life.The quantitative data were expressed as mean ± standard deviation,and t-test was used for comparison between groups,and while the count data were expressed as rate or composition ratio,and the x2 test was adopted for comparison between the groups.Logistic regression was used to examine the effect of possible factors (i.e.age and gender) on the prevalence of uncorrected refractive errors.Results A total of 6145 persons aged 50 years and above were enumerated and 5947 (96.8%) participants were examined,of whom 2388 had uncorrected refractive errors,with the prevalence of 40.2%.The prevalence of uncorrected refractive errors for myopia only,hyperopia only,astigmatism,and for hyperopia and astigmatism were 84.4%,84.2%,64.1% and 100%,respectively.Moreover,the higher prevalence of uncorrected refractive errors presented in elderly person (OR =1.07,P < 0.00l) and female (OR =1.38,P < 0.001),and education was a protective factor for junior high school (OR =0.74,P =0.003) and high school (OR =0.55,P < 0.001).Conclusion Uncorrected refractive errors presented high prevalence in rural population aged 50 years and above in Funing county,Jiangsu province,which are the leading cause of visual impairment.