1.Recent advance in relation of myeloperoxidase with stroke
Yihua ZHOU ; Xuerun LIU ; Mingjun GUO ; Yong GUAN ; Yinian ZHANG
Chinese Journal of Neuromedicine 2022;21(12):1290-1296
Stroke is the most common disease of the central nervous system, with high disability and mortality, which seriously affects the quality of life of patients and causes a huge disease burden. However, the overall treatment effect is still unsatisfied at present. Myeloperoxidase (MPO), a kind of peroxidase derived from neutrophils, may play an important role in stroke development through many ways, and has great potential in early diagnosis, clinical treatment and prognosis evaluation of stroke. This article reviews the research progress of MPO in stroke, aiming to provide new ideas for better diagnosis and treatment of stroke in clinic.
2.Research progress in retroauricular incision decompressive hemicraniectomy for the treatment of severe traumatic brain injury
Zhou QI ; Guoqiang LI ; Fan TIAN ; Zihao WEI ; Yinian ZHANG
Chinese Journal of Trauma 2022;38(7):661-665
Severe traumatic brain injury (sTBI) as the most common emergency severe syndrome in neurosurgery has a high mortality and poor prognosis. Decompressive craniectomy is the first treatment choice for sTBI. The reverse question mark incision was usually adopted in decompressive craniectomy, but some scholars also suggest using the n-type incision and Kempe incision. Although the curative effect is remarkable when using the above incisions, the incidence of postoperative complications is high, such as cerebrospinal fluid leakage, poor wound healing and flap ischemic necrosis. Moreover, the advantages and disadvantages of different incisions are not clear. Therefore, some scholars proposed retroauricular incision decompressive craniectomy for sTBI patients because this incision that retains blood supply through a new flap can provide better decompression effect and reduce incision-related complications. The authors review the research progress in retroauricular incision in aspects of the methods, indications and its advantages and disadvantages in constrast with other incisions, so as to provide a theoretical basis for the selection of incision for decompressive craniectomy in sTBI patients.
3.Phase I clinical trial of pharmacokinetics and safety comparison between the generic and the original bevacizumab
Xiuhua REN ; Hengyi YU ; Yinian FANG ; Donglin ZHANG ; Qian CHEN ; Yongfang LEI ; Dong LIU ; Zhelong LIU
Adverse Drug Reactions Journal 2022;24(6):300-307
Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.
4.Phase I clinical trial of pharmacokinetics and safety comparison between the generic and the original bevacizumab
Xiuhua REN ; Hengyi YU ; Yinian FANG ; Donglin ZHANG ; Qian CHEN ; Yongfang LEI ; Dong LIU ; Zhelong LIU
Adverse Drug Reactions Journal 2022;24(6):300-307
Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.
5.The relationship between histological classification of lung cancer and protein tyrosine phosphatase
Shangfu ZHANG ; Xueying SU ; Yinian LIU ; Jinling HAO ; Jufen ZHANG ; Niang CHENG ; Qinghua ZHOU
Chinese Journal of Lung Cancer 2001;4(1):66-69
Objective To investigate the relationship between histological classification of lung cancer and protein tyrosine phosphatase. Methods The expression of protein tyrosine phosphatase in bronchial epithelia from 34 patients with benign pulmonary lesions and 121 patients with primary pulmonary carcinoma was examined by immunohistochemical staining method. Results The positive rate of protein tyrosine phosphatase expression was 95.03%±2.10% in 34 patients with benign pulmonary lesions, 43.59%±14.41% in 121 patients with primary pulmonary carcinoma; 47.57%±16.26% in 46 patients with adenocarcinoma, 40.59%±14.04% in 48 patients with squamous cell carcinoma, 42.13%±9.84% in 27 patients with adenosquamous carcinoma; 31.63%±10.34% in 21 patients with poor differentiated squamous cell carcinoma, 41.39%±9.35% in 18 patients with intermediate differentiated squamous cell carcinoma, 59.90%±8.61% in 9 patients with well differentiated squamous cell carcinoma; 34.14%±12.53% in 16 patients with poor differentiated adenocarcinoma, 52.10%±12.19% in 26 patients with intermediate differentiated adenocarcinoma, and 63.05%±15.84% in 4 patients with well differentiated adenocarcinoma. A significant difference of protein tyrosine phosphatase positive expression was observed between benign pulmonary lesions and primary pulmonary carcinomas, and between poor differentiated primary pulmonary carcinomas and well differentiated primary pulmonary carcinomas (P<0.01 or P<0.05). Conclusion Detection of protein tyrosine phosphatase may be helpful to differentiate pulmonary lesions from lung cancer and be regarded as one of the indices in predicting the prognosis of patients with primary pulmonary carcinomas.

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