1.Clinical characteristics of patients with paraquat mixed with diquat poisoning
Xiaorong CHEN ; Xiaoying DU ; Huanle YE ; Hu TANG ; Yahui TANG ; Longwang CHEN ; Jie LIAN ; Bin WU ; Guangju ZHAO ; Zhongqiu LU
Chinese Journal of Emergency Medicine 2023;32(2):203-209
Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.
2.PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.
Xin-Xing DU ; Yan-Hao DONG ; Han-Jing ZHU ; Xiao-Chen FEI ; Yi-Ming GONG ; Bin-Bin XIA ; Fan WU ; Jia-Yi WANG ; Jia-Zhou LIU ; Lian-Cheng FAN ; Yan-Qing WANG ; Liang DONG ; Yin-Jie ZHU ; Jia-Hua PAN ; Bai-Jun DONG ; Wei XUE
Asian Journal of Andrology 2023;25(2):179-183
Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male
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Humans
;
Prostate-Specific Antigen
;
Treatment Outcome
;
Prostatic Neoplasms, Castration-Resistant/drug therapy*
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Retrospective Studies
3.Use of anticoagulant mechanical methods after laparoscopic sleeve gastrectomy for obese patients
Kai LI ; Chen LIU ; Nengwei ZHANG ; Jirun PENG ; Bin ZHU ; Dexiao DU ; Dongbo LIAN ; Dongdong ZHANG ; Ke GONG
Chinese Journal of General Surgery 2022;37(1):39-43
Objective:To investigate anticoagulant effects of mechanical methods in obese patients undergoing laparoscopic sleeve gastrectomy (LSG).Methods:In this prospective study, 54 obese patients receiving LSG were enrolled . All patients were given post-op mechanical methods for thrombogenic interventions. BMI and the operation-related factors were recorded. Venous blood specimens were taken from each patient before surgery, at the end of pneumoperitoneum (i.e., 0 h after surgery), at 24 hours after surgery for prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer (D-D).Results:All 54 obese patients successfully underwent LSG. No severe complications were observed. Before operation, the mean BMI was (43.49±8.29) kg/m 2. DVT-2600 device was applied in all patients for 3 consecutive days after surgery. The PT values increased at 0 h, 24 h after surgery [(12.4±1.2) s, (12.4±0.8) s vs. (11.2±0.8) s, P=0, 0]. The APTT values at 0 h, 24 h after surgery decreased [(29.7±3.6) s, (29.0±3.1) s vs.(31.2±3.3) s, P=0.020, 0.001]. However, the D-D values increased at 0 h,24 h after operation [(213±143) ng/ml ,(445±237) ng/ml vs. (85±108) ng/ml, P=0, 0]. All patients were followed up for 1 month, and no thrombosis -related complications were observed. Conclusion:Mechanical methods for obese patients after LSG can help decrease the risk of deep venous thrombosis.
4.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
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Brain Abscess
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Child
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Child, Preschool
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Escherichia coli
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Female
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Humans
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Hydrocephalus
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Infant
;
Infant, Newborn
;
Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
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Streptococcus agalactiae
;
Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
5.Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.
Yuan-Kai SHI ; Xiao-Nan HONG ; Jian-Liang YANG ; Wei XU ; Hui-Qiang HUANG ; Xiu-Bin XIAO ; Jun ZHU ; Dao-Bin ZHOU ; Xiao-Hong HAN ; Jian-Qiu WU ; Ming-Zhi ZHANG ; Jie JIN ; Xiao-Yan KE ; Wei LI ; De-Pei WU ; Shen-Miao YANG ; Xin DU ; Yong-Qian JIA ; Ai-Chun LIU ; Dai-Hong LIU ; Zhi-Xiang SHEN ; Lian-Sheng ZHANG ; Leonard JAMES ; Edward HELLRIEGEL
Chinese Medical Journal 2021;134(11):1299-1309
BACKGROUND:
Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.
METHODS:
This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.
RESULTS:
A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.
CONCLUSION:
Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult
;
Antineoplastic Combined Chemotherapy Protocols
;
Bendamustine Hydrochloride/therapeutic use*
;
China
;
Humans
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Lymphoma, Non-Hodgkin/drug therapy*
;
Neoplasm Recurrence, Local/drug therapy*
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Prospective Studies
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Rituximab/therapeutic use*
6.A long-term result of laparoscopic Roux-en-Y gastric bypass vs.laparoscopic sleeve gastrectomy in the treatment of obese patients with type 2 diabetes mellitus
Dexiao DU ; Ke GONG ; Bin ZHU ; Dongbo LIAN ; Qing FAN ; Peirong TIAN ; Nengwei ZHANG
Chinese Journal of General Surgery 2019;34(2):100-104
Objective To compare laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy for the treatment of obese patients with type 2 diabetes mellitus.Methods A retrospective analysis of T2DM patients with LRYGB (28 cases) and LSG (35 cases) was enrolled from Jan 2010 to Jun 2013.Results The indicator such as BMI,fasting glucose,fasting insulin,HbA1c,and insulin resistance were significantly lower in 1 year,3 years and 5 years after operation [LRYGB group:(37.3 ±3.7) kg/m2 to (32.3 ± 3.4) kg/m2 to (28.8 ± 3.0) kg/m2 to (25.5 ± 2.8) kg/m2,t =13.670,15.499,21.710,P=0.000,0.000,0.000;(8.2 ± 1.8) mmol/L to (6.0 ± 1.3) mmol/L to (5.2 ±0.9) mmol/L to (4.7±0.5) mmol/L,t =6.664,8.723,10.282,P=0.000,0.000,0.000;(32.2±17.0) μ IU/ml to (16.1 ± 12.1) μIU/ml to (8.6 ±5.2) μ IU/ml to (5.2 ±2.8) μIU/ml,t =7.453,8.218,8.687,P =0.000,0.000,0.000;(7.4% ±0.6%) to (6.2% ±0.7%) to (5.7% ±0.7%) to (5.1% ±0.6%),t =11.362,18.771,21.186,P=0.000,0.000,0.000;(12.0±7.3) to (4.6±4.3) to (2.1 ±1.7) to (1.1 ±0.7),t =6.455,7.667,8.050,P=0.000,0.000,0.000;LSG group:(39.2±5.2) kg/m2 to (34.1 ±4.5) kg/m2to (29.3±4.0) kg/m2to (25.1 ±2.3) kg/m2,t=11.676,13.680,19.161,P=0.000,0.000,0.000;(8.0±2.9) mmol/L to (5.8±1.5) mmol/L to (5.1 ±0.9) mmol/L to (4.6 ±0.5) mmoL/L,t=5.467,6.921,7.741,P=0.000,0.000,0.000;(29.1 ±25.2) μIU/ml to (16.4±10.6) μ IU/ml to (8.8±5.5) μ IU/ml to (5.5 ±2.0) μIU/ml,t =3.512,5.232,5.702,P=0.001,0.000,0.000;(7.7% ±1.3%) to (6.3% ±0.6%) to (5.8% ±0.6%) to (5.2% ±0.6%),t=8.001,10.106,11.922,P =0.000,0.000,0.000;(9.8 ±9.6) to (3.9 ±2.2) to (1.9 ±1.0) to (1.1 ± 0.4),t =3.733,4.972,5.404,P =0.001,0.000,0.000].There was no significant difference between the two groups in 1 year,3 year and 5 year post-operation (DM remission:71% to 69%,89% to 80%,93% to 89%) (P > 0.05).Conclusion LRYGB and LSG have the same long-term efficacy for T2DM patients.
7.Ultrasound Assessment of Intima-media Thickness and Diameter of Carotid Arteries in Patients Undergoing Hemodialysis or Renal Transplantation
Zhao-Jun LI ; Lian-Fang DU ; QIN YAN ; Ji-Bin LIU ; Xiang-Hong LUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2018;38(4):727-733
Renal transplant (RT) recipients have a high risk of developing cardiovascular diseases.However,the effects of renal transplantation on the development of arteriosclerosis have been controversial.The carotid intima-media thickness (CIMT) and diameter (CD) are important indicators of vascular remodeling and arteriosclerosis.In this study,31 patients with hemodialysis (HD),31 RT recipients and 84 age-and gender-matched control subjects were enrolled.Their CIMT and CD were measured by ultrasonic radiofrequency tracking,and the linear regression models and Z test were used to identify the progression of arteriosclerosis and the risk factors.Compared with HD group,RT group had significantly lower CIMT and CD.CIMT was found to be associated with age,body weight,resistance index and diastolic velocity,while CD was associated significantly with age,body weight,pulsatility index,end diastolic velocity and diastolic blood pressure (DBP),respectively.The correlation curves between CIMT and age showed the slopes of curves were decreased successively in control,RT and HD groups,and the curves between CD and age showed the slopes were decreased in order of RT > control > HD groups.It was concluded that CIMT and CD were significantly correlated with age in RT and moderately with age in HD patients.RT could reduce the progress of arteriosclerosis in patients with end-stage renal disease.
8.Relationship between quantitative indices of carotid plaque from contrast-enhanced ultrasound and leukocytes in patients with acute large artery atherosclerotic stroke
jun Zhao LI ; bin Wan LI ; Yun BAI ; Qing YANG ; fang Lian DU ; hong Xiang LUO
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(12):1640-1643
Objective·To investigate the relationship between quantitative indices of carotid plaques from contrast-enhanced ultrasound and leukocytes, and explore the value in the patients with acute large artery atherosclerotic stroke (LAAS). Methods·A total of 62 patients with LAAS and 48 matched control subjects hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University from June 2016 to June 2017 were enrolled. Obvious carotid plaques were examined by contrast-enhanced ultrasound. The parameters of time-intensity curve i.e. peak (PTIC) and mean (MTIC), and the parameters of fitting curve i.e. peak (PFC), sharpness (SFC), and under the curve area (AUCFC) were obtained. These parameters were compared between the groups using two samples t tests. The correlations between the parameters and leukocyte counts were analyzed by Pearson correlation analysis. Results·① In LAAS group, the total leukocyte and neutrophil counts were higher than those of the control group, while the lymphocyte count was lower than that of the control group (P<0.05). ② The PTIC, MTIC, PFC, SFC and AUCFC were significantly larger in LAAS group than those in the control group, respectively (P<0.05).③ PTIC, MTIC and PFC were negatively correlated with lymphocytes, respectively (r=-0.291, -0.263 and -0.270, P<0.05). SFC and AUCFC were positively correlated with neutrophils, respectively (r=0.261 and 0.298, P<0.05). Conclusion·Quantitative indices of carotid plaques from contrast-enhanced ultrasound are associated with circulating leukocytes, and the association helps assess the vulnerability of the plaques.
9.Effect of FTO gene on type 2 diabetes mellitus treated by Roux-en-Y gastric bypass
Dexiao DU ; Ke GONG ; Bin ZHU ; Dongbo LIAN ; Qing FAN ; Guangzhong XU ; Nengwei ZHANG
Chinese Journal of General Surgery 2017;32(12):1050-1053
Objective To investigate the effect of FTO gene on laparoscopic Roux-en-Y gastric bypass for type 2 diabetes.Methods From Jan 2014 to 2015 Jun,32 T2DM patients received LRYGB in Beijing Shijitan Hospital.According to single nucleotide polymorphism of FTO rs9939609 gene,patients were divided into TF genotype (20 cases),and AT/AA genotype (12 cases).Results Following the degression of BMI from (36.4 ±3.3) kg/m2 to (28.1 ±2.8) kg/m2,fasting blood glucose and HbA1c in group A significantly improved [(8.9 ± 1.6) mmol/L vs.(5.6 ± 1.2) mmol/L,t =8.274,P =0.000;(8.5% ± 1.9%) vs.(6.2% ± 0.8%),t =5.032,P =0.000].Following the degression of BMI from (39.5 ±5.6) kg/m2 to (29.7 ± 5.1) kg/m2,fasting blood glucose and HbA1c in group B significantly improved [(10.8 ± 2.8) mmol/L vs.(4.9 ± 0.6) mmol/L,t =7.589,P =0.000;(9.0% ± 1.8%) vs.(6.1% ±0.9%),t =5.324,P =0.000].Insulin resistance index in both groups significantly improved [(12.6±10.7) vs.(4.9±5.6),t=5.402,P=0.000;(16.0±5.6) vs.(1.7±1.3),t=9.025,P=0.000].Fasting blood glucose and the insulin resistance index in group B patients was significantly lower than that in group A patients (P < 0.05).Conclusion T2DM patients with FTO rs9939609 gene phenotype AT/AA have better prognosis than those with TT in postoperative diabetes improvement.
10.Anti-tumor effects of vascular endothelial growth factor fusion protein vaccine modified by a molecular adjuvant
Lin GUO ; Mei-Yu LU ; Ling ZHOU ; Min LI ; Yu-Wei LIU ; Bin-Lian DU ; Qing-Shou YAO ; Mao-Lei XU
The Chinese Journal of Clinical Pharmacology 2017;33(13):1225-1228
Objective To investigate whether 2 repeats of mycobacterial microbial hot shock protein 70 (HSP70) 407-426 (2mHSP70407-426,M2) could act as an effective molecular adjuvant to enhance the anti-tumor efficiency of vascular endothelial growth factor (VEGF) fusion protein vaccine.Methods The gene encoding two tandem repeat sequences of HSP70407-426 was introduced to the terminus of the constructed hVEGF121 mutant 1 gene to prepare a recombined hVEGF121 mutant 2 protein vaccine by PCR technique.The anti-tumor efficacy of hVEGF121 mutant 2 protein vaccine was investigated using a H22 liver cancer subcutaneous tumor model.The 24 mice were randomly divided into three groups:model group,experiment 1 group (80 μg hVEGF121 mutant 1 protein) and experiment 2 group (80 μg hVEGF121 mutant 2 protein).The humoral and cellular immune responses were detected by ELISA and splenic lymphocyte proliferation assay.The anti-angiogenesis effect was evaluated by an intradermal tumor model.Results The tumor weight of the experimental 1 group and the experimental 2 group were (1.17± 0.25) g and (1.58 ± 0.28) g.Compared with the experimental 1 group,the tumor weight of tumor bearing mice in the experimental 2 group was lower significanfly(P <0.05).The anti-VEGF antibodies of the experimental 1 group and experimental 2 group was 0.54 ± 0.09,0.74 ± 0.1.Compared with experimental 1 group,higher titers of anti-VEGF antibody were detected in immune serum of the experimental 2 group with statistically significant(P <0.05).The proliferative activity of spleen lymphocytes in the experimental 1 group and the experimental 2 group was 0.26 ±0.03,0.36 ±0.04.Compared with the experimental 1 group,the vaccine immunization in experimental 2 group can stimulate the proliferation of spleen lymphocytes more effectively with statistically significant (P < 0.05).Conclusion M2 could act as an effective adjuvant to help VEGF fusion protein vaccine to elicit a strong anti-tumor efficacy.

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