1.Establishment of animal models of cervical instability and vertebral artery ischemia
Shengjie ZHU ; Fang ZHU ; Zongjin YUE ; Zihua WANG
Chinese Journal of Tissue Engineering Research 2014;(27):4418-4422
BACKGROUND:Cervical spondylosis refers to cervical intervertebral spondylotic myelopathy and secondary degenerative changes, as wel as pathological changes in surrounding tissue structures. Establishing animal model of cervical instability and vertebral-basilar artery ischemia is the key in the studies addressing cervical spondylosis pathophysiology and treatment.
OBJECTIVE:To establish animal model of unstable cervical spine and vertebral-basilar artery ischemia, and explore new progress of animal model imitation study.
METHODS:A computer-based retrieval of PubMed database and CNKI database was performed for articles published from 1979 to 2012. The key words were“cervical instability, basal-vertebral artery ischemia, animal model”in English and Chinese. The articles about cervical instability, basal-vertebral artery ischemia, and animal model were screened, and those published recently or in authorized journals were preferred in the same field. Final y 43 articles were included in this study.
RESULTS AND CONCLUSION:An ideal animal model of cervical disease is needed. Animal model of cervical diseases is often used for the study of disease causes, onset mechanism and biochemistry. As the causes and mechanism of cervical diseases remain unclear, the existing modeling method cannot duplicate human cervical diseases, so further studies are needed to explore the establishment of models, positive rate and modeling time.
2.Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog.
Zihua ZHENG ; Xiaoxia ZHU ; Hui GAN ; Ruolan GU ; Zhuona WU ; Zhiyun MENG ; Guifang DOU
Acta Pharmaceutica Sinica 2013;48(8):1307-11
Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
3.Analysis of incidence and influencing factors of R-CHOP-like regimen treatment-related interstitial pneumonia in B-cell non-Hodgkin lymphoma
Hong ZHENG ; Ran CUI ; Xuelian LI ; Zihua ZHU
Journal of Leukemia & Lymphoma 2020;29(7):405-409
Objective:To explore the related influencing factors of interstitial pneumonia (IP) in B-cell non-Hodgkin lymphoma (B-NHL) patients treated with R-CHOP-like chemotherapy regimen.Methods:The clinical data of 377 CD20 + B-NHL patients in Minhang Branch of Fudan University Shanghai Cancer Hospital from January 2014 to June 2019 were retrospectively analyzed. According to whether rituximab was used, patients were divided into R-CHOP-like chemotherapy group (275 cases) and CHOP-like chemotherapy group (102 cases). The incidence of IP in patients stratified according to different clinical factors was analyzed, and logistic multivariate regression was used to analyze the risk factors of IP. Results:Thirty-eight out of 377 patients (10.08%) developed IP; the incidence rates of IP in the R-CHOP-like chemotherapy group and the CHOP-like chemotherapy group were 13.09% (36/275) and 1.96% (2/102), respectively, and the difference was statistically significant (χ 2 = 10.169, P < 0.01). There were statistical differences in the incidence rates of IP between patients with or without rituximab, with or without liposomal doxorubicin in the regimen, and with or without grade Ⅳ neutropenia occurred during the treatment [13.09% (36/275) vs. 1.96% (2/102), 18.18% (22/ 121) vs. 6.25% (16/256), 15.43% (27/175) vs. 5.45% (11/202), all P < 0.01]. Logistic regression analysis showed that the application of rituximab ( OR = 6.761, 95% CI 1.369-33.711, P = 0.020) and grade Ⅳ neutropenia ( OR = 7.443, 95% CI 2.132-8.199, P = 0.001) were independent risk factors for the occurrence of IP. Conclusions:R-CHOP-like chemotherapy regimen increases the occurrence of IP in patients with B-NHL. The use of rituximab and grade Ⅳ neutropenia are independent risk factors for the occurrence of IP.
4. A multicenter study of reference intervals for 15 laboratory parameters in Chinese children
Xuhui ZHONG ; Jie DING ; Jianhua ZHOU ; Zihua YU ; Shuzhen SUN ; Ying BAO ; Jianhua MAO ; Li YU ; Zhihui LI ; Ziming HAN ; Hongmei SONG ; Xiaoyun JIANG ; Yuling LIU ; Bili ZHANG ; Zhengkun XIA ; Chunhua JIN ; Guanghua ZHU ; Mo WANG ; Shipin FENG ; Ying SHEN ; Songming HUANG ; Qingshan MA ; Haixia LI ; Xuejing WANG ; Kiyoshi ICHIHARA ; Chen YAO ; Chongya DONG
Chinese Journal of Pediatrics 2018;56(11):835-845
Objective:
To establish comprehensive laboratory reference intervals for Chinese children.
Methods:
This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex.
Results:
In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old.
Conclusion
This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.
5.Analysis of serum allergen-specific immunoglobulin E in 3 051 patients with eczema or dermatitis in an allergy clinic
Fanping YANG ; Li MA ; Sheng′an CHEN ; Zihua CHEN ; Lanting WANG ; Zhen ZHANG ; Ying ZHAO ; Qinyuan ZHU ; Yu XU ; Lin TANG ; Yao HU ; Xiaoqun LUO
Chinese Journal of Dermatology 2023;56(2):136-141
Objective:To analyze measurement results of serum allergen-specific immunoglobulin E (IgE) in patients with eczema/dermatitis.Methods:A retrospective analysis was conducted on serum allergen-specific immunoglobulin E (IgE) levels in 3 051 patients with eczema/dermatitis, who visited the allergy clinic of Huashan Hospital from April 1, 2021 to March 31, 2022. The serum allergen-specific IgE level was detected by using the Phadia allergen detection system, and positive rates of allergens were calculated to determine common inhaled allergens and food allergens in patients with eczema/dermatitis. Comparisons of enumeration data between groups were performed by chi-square test.Results:Among the 3 051 patients with eczema/dermatitis, there were 1 412 with atopic dermatitis and 1 639 were other eczema/dermatitis. Detection of serum allergen-specific IgE showed that 1 629 (53%) patients were positive for allergens, and the number of positive allergen-specific IgEs in each patient was 3.0 ± 1.6. The top 3 common inhaled allergens in patients with eczema/dermatitis were Dermatophagoides farinae (904/1 522, 59%) , Dermatophagoides pteronyssinus (891/1 513, 59%) and Alternaria alternata (206/1 068, 19%) , and the top 3 common food allergens were shrimps (251/1 432, 18%) , egg white (165/992, 17%) and cow milk (149/994, 15%) . Among the 3 051 patients, 25 (1%) were aged < 2 years, 571 (19%) aged 2 - 12 years, 285 (9%) aged 12 - 18 years, and 2 170 (71%) were aged > 18 years. The most common food allergens were both egg white in the age groups of < 2 years and 2 -12 years (77%, 37%, respectively) , and were both shrimps in the age groups of 12 - 18 years and > 18 years (31%, 17%, respectively) . Dermatophagoides pteronyssinus and Dermatophagoides farina were the top 2 common inhaled allergens in all age groups, with the positive rate ranging from 36% to 84%; in addition, the positive rate of molds was relatively high in the age group of 2 - 12 years (mold mixture: 37%; Alternaria alternata: 27%) . From April 2021 to March 2022, the positive rate of outdoor allergens ranged from 10% to 15% among outpatients in every month; the positive rates of tree pollen and grass pollen increased from April 2021, and peaked in October 2021. The patients with atopic dermatitis showed a significantly increased positive rate of allergens (73%) compared with those with other eczema/dermatitis (37%, χ2 = 389.36, P<0.001) , and the rank of common allergens in the patients with atopic dermatitis was basically the same as that in those with eczema/dermatitis. Conclusions:The common allergens were Dermatophagoides farina, Dermatophagoides pteronyssinus and Alternaria alternata in the patients with eczema/dermatitis. Food allergy was more common in infant patients, and inhalation allergy was more common in child, adolescent and adult patients. The positive rate of allergen-specific IgEs was markedly higher in the patients with atopic dermatitis than in those with other eczema/dermatitis.
6.Front-line therapy for brain metastases and non-brain metastases in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: a network meta-analysis.
Yixiang ZHU ; Chengcheng LIU ; Ziyi XU ; Zihua ZOU ; Tongji XIE ; Puyuan XING ; Le WANG ; Junling LI
Chinese Medical Journal 2023;136(21):2551-2561
BACKGROUND:
The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses.
METHODS:
Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework.
RESULTS:
This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively.
CONCLUSION
Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans
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Carcinoma, Non-Small-Cell Lung/metabolism*
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Afatinib/therapeutic use*
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Lung Neoplasms/metabolism*
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Bevacizumab/therapeutic use*
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Bayes Theorem
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Network Meta-Analysis
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Protein Kinase Inhibitors/therapeutic use*
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Pemetrexed/therapeutic use*
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ErbB Receptors/genetics*
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Brain Neoplasms/genetics*
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Mutation/genetics*