Objective:To study the effect of Wuzhi capsules on tacrolimus trough concentration in kidney transplant recipients with different CYP3A5 genotypes.Methods:From June 2015 to October 2019, 162 patients who underwent renal transplantation for the first time were retrospectively analyzed. The patients were divided into two groups, combined and uncombined, according to whether combined with Wuzhi capsules. There were 81 cases in the uncombined group (55 males and 26 females), and 81 in the combined group (62 males and 19 females). There was no significant difference between the two groups( P=0.219). The ages of the uncombined group and the combined group were (39.26±11.91) years old and (37.21±10.88) years old ( P=0.103), the weights were (62.39±11.64) kg and (66.18±13.89)kg ( P=0.298), systolic blood pressure were (147.28±20.24) mmHg and (145.00±16.42) mmHg (1 mmHg=0.133 kPa)( P=0.276), diastolic blood pressure were (92.25±13.87) mmHg and (92.20±12.53) mmHg ( P=0.886), alanine aminotransferase were (12.24±8.59) U/L and (17.06±13.11) U/L ( P=0.015), aspartate aminotransferase were (17.76±9.12) U/L and (16.57±8.37) U/L ( P=0.463), fasting blood glucose were (8.70±3.48) mmol/L and (7.18±2.74)mmol/L ( P=0.006), hemoglobin were (98.96±17.53) g/L and (101.05±18.67) g/L ( P=0.789), creatinine were (665.22±296.55) μmol/L and (797.32±279.32) μmol/L ( P=0.007), estimated glomerular filtration rate were (11.47±14.11) ml/(min·1.73m 2) and (8.85±3.71) ml/(min·1.73m 2) ( P=0.130)in the kidney transplant recipients before surgery. Among the 162 cases in this study, there were 86 cases (53.09%) of CYP3A5*1*3 genotype, 17 cases (10.49%) of CYP3A5*1*1 genotype, 59 cases (36.42%) of CYP3A5*3*3 genotype, and the minimum allele frequency of CYP3A5*1 was 37.04%. In the uncombined group, CYP3A5*1*3 genotype 39 cases (48.15%), CYP3A5*1*1 genotype 5 cases (6.17%), and CYP3A5*3*3 genotype 37 cases (45.68%). In the combined group, CYP3A5*1*3 genotype 47 cases (58.02%), CYP3A5*1*1 genotype 12 cases (14.81%), and CYP3A5*3*3 genotype 22 cases (27.16%), with statistically significant differences in the two groups ( P=0.024). The patients were treated with a triple immunosuppressive regimen (tacrolimus+ mycophenolate mofetil+ glucocorticoid) based on tacrolimus [initial dose: 0.15-0.30 mg/(kg·d)], combination of Wuzhi capsules in the combination group (11.25 mg, twice a day). The trough concentration of tacrolimus was detected by enzyme-linked immunosorbent assay, compare the difference in the trough concentration of tacrolimus between the two groups. The relationship between the effect of Wuzhi capsules and CYP3A5 gene polymorphism was compared, and compare the changes before and after the application of CYP3A5 genotype combined with Wuzhi Capsules. The influencing factors of tacrolimus trough concentration were analyzed by multiple linear regression. Results:In the combined with Wuzhi capsules, the dose corrected trough concentration (C 0/D) of tacrolimus was higher than that in patients without Wuzhi capsules, and the extent of increase was related to genotype. The C 0/D of tacrolimus in patients with CYP3A5*3*3 genotype in the combination and non-combination groups were (12.15±2.95) (ng·ml -1/0.1mg·kg -1·d -1) and (9.99±2.33) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.004), CYP3A5*1*3 genotype were (11.11±3.20) (ng·ml -1/0.1mg·kg -1·d -1) and (6.86±1.62) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001), and there were significant difference. However, CYP3A5*1*1 genotype were(8.29±2.64) (ng·ml -1/0.1mg·kg -1·d -1) and (6.16±2.87) (ng·ml -1/0.1mg·kg -1·d -1) ( P=0.160), there was no significant difference. The tacrolimus C 0/D of the combined group before and after the Wuzhi capsule were as follows: CYP3A5*3*3 genotype: (7.18±2.33)(ng·ml -1/0.1mg·kg -1·d -1) and (13.33±3.09) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*3 genotype: (5.14±2.14) (ng·ml -1/0.1mg·kg -1·d -1) and (10.61±3.20) (ng·ml -1/0.1mg·kg -1·d -1) ( P<0.001); CYP3A5*1*1 genotype: (5.17±3.75) (ng·ml -1/0.1mg·kg -1·d -1) and (8.31±2.74) (ng·ml -1/0.1mg·kg -1·d -1)( P=0.002), and the differences were statistically significant. The results of multiple linear regression showed that the combination of Wuzhi capsules (β=0.508, P<0.001) and CYP3A5 genotype(CYP3A5*1*3 and CYP3A5*3*3: β=-0.361, P<0.001; CYP3A5*1*1 and CYP3A5*3*3: β=-0.425, P<0.001)could influence the trough concentration. The sex (β=-0.100, P=0.124) and age (β=-0.003, P=0.967) of renal transplant recipients had no statistical significance to tacrolimus C 0/D. Conclusions:In the renal transplant patients, CYP3A5 genotype and combined use of Wuzhi capsules are the main factors affecting tacrolimus C 0/D. In order to achieve the expected trough concentration as soon as possible, the interaction between CYP3A5 genotypes and drug combination should be considered.

Objective:To explore the risk factors of myelosuppression caused by nedaplatin in patients with lung cancer.Methods:The medical records of postoperative patients with advanced lung cancer and receiving nedaplatin-based chemotherapy in Shandong Provincial Qianfoshan Hospital from June 2015 to August 2018 were searched using hospital information system and analyzed retrospectively. According to sex, age (<60 years old, ≥ 60 years old), glutathione mercaptotransferase (GSTP) 1A313G genotype (AA or AG), pathological classification (non-small cell lung cancer, small cell lung cancer), having smoking history or not, being with or without liver injury and kidney injury, the patients were divided into 2 groups, respectively. The overall myelosuppression incidence and incidences of myelosuppression with different manifestations and different degrees were compared respectively between each 2 groups of patients with above-mentioned 7 different clinical features. The risk factors of nedaplatin-induced myelosuppression were analyzed using logistic regression.Results:A total of 46 patients were enrolled, including 34 males and 12 females. Among the 46 patients, 30 cases developed myelosuppression after administration of nedaplatin, and the overall incidence of myelosuppression was 65.2%, including 20 cases of grade Ⅰ-Ⅱ (43.5%) and 10 cases of grade Ⅲ-Ⅳ (21.7%). After administration of nedaplatin, the incidence of severe myelosuppression in patients with small cell lung cancer (3/5) was higher than that with non-small cell lung cancer (17.1%) ( P<0.05), showed by the univariate analysis; the overall incidence of leukopenia in males was higher than that in females (58.8% vs. 25.0%); the overall incidence of leukopenia and neutropenia was higher in patients with smoking history than that in patients without previous smoking history (68.0% vs. 28.6%, 0.01%, P=0.01; 64.0% vs. 33.3%, P=0.04); the overall incidence of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer (4/5 vs. 9.8%, P<0.01); the differences in the incidences of different degrees of neutropenia in patients with and without smoking history were statistically significant ( P=0.03); the differences in the incidences of different degrees of leukopenia, neutropenia, and thrombocytopenia in patients with different pathological classification were statistically significant ( P<0.01 for all). The binary logistic regression analysis showed that the risk of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer ( OR=25.00, 95 %CI:2.20-284.61, P=0.01). The orderial logistic regression analysis showed that a pathological classification of small cell lung cancer was a risk factor for severe myelosuppression, leukopenia, neutropenia, and thrombocytopenia ( OR=13.20, 95 %CI: -4.67-0.49, P=0.02; OR=22.20, 95 %CI: -5.37-0.83, P=0.01; OR=19.49, 95 %CI: -5.11-0.82, P=0.01; OR=13.87, 95 %CI: -4.89-0.38, P=0.02). Conclusions:A pathological classification of small cell lung cancer is an independent risk factor for severe myelosuppression in lung cancer patients after taking nedaplatin. Male patients with a history of smoking are more likely to have leukopenia/neutropenia.

Objective:To explore the risk factors of myelosuppression caused by nedaplatin in patients with lung cancer.Methods:The medical records of postoperative patients with advanced lung cancer and receiving nedaplatin-based chemotherapy in Shandong Provincial Qianfoshan Hospital from June 2015 to August 2018 were searched using hospital information system and analyzed retrospectively. According to sex, age (<60 years old, ≥ 60 years old), glutathione mercaptotransferase (GSTP) 1A313G genotype (AA or AG), pathological classification (non-small cell lung cancer, small cell lung cancer), having smoking history or not, being with or without liver injury and kidney injury, the patients were divided into 2 groups, respectively. The overall myelosuppression incidence and incidences of myelosuppression with different manifestations and different degrees were compared respectively between each 2 groups of patients with above-mentioned 7 different clinical features. The risk factors of nedaplatin-induced myelosuppression were analyzed using logistic regression.Results:A total of 46 patients were enrolled, including 34 males and 12 females. Among the 46 patients, 30 cases developed myelosuppression after administration of nedaplatin, and the overall incidence of myelosuppression was 65.2%, including 20 cases of grade Ⅰ-Ⅱ (43.5%) and 10 cases of grade Ⅲ-Ⅳ (21.7%). After administration of nedaplatin, the incidence of severe myelosuppression in patients with small cell lung cancer (3/5) was higher than that with non-small cell lung cancer (17.1%) ( P<0.05), showed by the univariate analysis; the overall incidence of leukopenia in males was higher than that in females (58.8% vs. 25.0%); the overall incidence of leukopenia and neutropenia was higher in patients with smoking history than that in patients without previous smoking history (68.0% vs. 28.6%, 0.01%, P=0.01; 64.0% vs. 33.3%, P=0.04); the overall incidence of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer (4/5 vs. 9.8%, P<0.01); the differences in the incidences of different degrees of neutropenia in patients with and without smoking history were statistically significant ( P=0.03); the differences in the incidences of different degrees of leukopenia, neutropenia, and thrombocytopenia in patients with different pathological classification were statistically significant ( P<0.01 for all). The binary logistic regression analysis showed that the risk of thrombocytopenia in patients with small cell lung cancer was higher than that with non-small cell lung cancer ( OR=25.00, 95 %CI:2.20-284.61, P=0.01). The orderial logistic regression analysis showed that a pathological classification of small cell lung cancer was a risk factor for severe myelosuppression, leukopenia, neutropenia, and thrombocytopenia ( OR=13.20, 95 %CI: -4.67-0.49, P=0.02; OR=22.20, 95 %CI: -5.37-0.83, P=0.01; OR=19.49, 95 %CI: -5.11-0.82, P=0.01; OR=13.87, 95 %CI: -4.89-0.38, P=0.02). Conclusions:A pathological classification of small cell lung cancer is an independent risk factor for severe myelosuppression in lung cancer patients after taking nedaplatin. Male patients with a history of smoking are more likely to have leukopenia/neutropenia.