Prenatal diagnosis and genetic counseling in two pedigrees affected with infantile polycystic kidney disease due to PKHD1 gene mutations / 中华医学遗传学杂志

OBJECTIVE@#To detect potential mutations of the PKHD1 gene in two pedigrees affected with infantile polycystic kidney disease.@*METHODS@#Clinical data and peripheral venous blood samples were collected from the probands and their parents as well as fetal amniotic fluid cells. Genome DNA was extracted from the peripheral blood samples and amniotic fluid cells. Exons 32 and 61 of the PKHD1 gene were amplified with PCR and subjected to direct sequencing.@*RESULTS@#The proband of pedigree 1 was found to carry c.4274T>G (p.Leu1425Arg) mutation in exon 32 and c.10445G>C (p.Arg3482Pro) mutation in exon 61 of the PKHD1 gene, which were inherited from her father and mother, respectively. The fetus has carried the c.4274T>G (p.Leu1425Arg) mutation. In pedigree 2, the wife and her husband had respectively carried a heterozygous c.5979_5981delTGG mutation and a c.9455delA mutation of the PKHD1 gene. No chromosomal aberration was found in the umbilical blood sample, but the genetic testing of their fetus was failed. Based on software prediction, all of the 4 mutations were predicted to be pathogenic.@*CONCLUSION@#PKHD1 c.4274T>G (p.Leu1425Arg), c.10445G>C (p.Arg3482Pro), c.5979_5981delTGG and c.9455delA were likely to be pathogenic mutations. The results have facilitated genetic counseling and prenatal diagnosis for the two pedigrees.

Expression of vascular relevant factors in rabbits with deep Ⅱ degree burn based on the Notch signaling pathway / 中南大学学报(医学版)

Objective:To investigate the relationship between the Notch signaling pathway and expression of vascular relevant factors in rabbit deep Ⅱ degree burn model.Methods:A total of 120 New Zealand white rabbits were randomly divided into a block group,a model group,and a control group,The block group was injected 2 mg/kg γ-secretase inhibitor (GSI) once a day at 1 d before the model establishment,and 1-14 d after the deep Ⅱ degree burns model establishment.The model group were injected physiological saline at the same time.The control group was only injected with the same amount of saline.The expressions of vascular endothelial growth factor (VEGF),vascular endothelial growth factor receptor 2 (VEGFR-2),matrix metalloprotein 2 (MMP-2) and matrix metalloprotein 9 (MMP-9) were detected by immunohistochemistry.Results:The expressions of VEGF and VEGFR-2 in the model group and the block group were significantly increased within 21 days after modeling,while decreased after 21 days;the expressions of MMP-2 and MMP-9 were decreased within 21 days after modeling,while increased after 21 days,with significant differences compared with the control group (P＜0.05).The expressions of VEGF and VEGFR-2 in the model group were higher than that in the block group,and the expressions of MMP-2 and MMP-9 were lower than those in the block group (P＜0.05).The expression of VEGFR-2 was positively correlated with VEGF,while MMP-2 and MMP-9 were negatively correlated with VEGF within 21 days after modeling.Conclusion:In the rabbit deep Ⅱ degree burn model,the Notch signaling pathway was blocked to attenuate the expressions of VEGF and VEGFR-2,and to up-regulate the expressions of MMP-2 and MMP-9.

Observation on the curative effect of small ring electrode assisted LEEP of cervix in treatment of cervical erosion with cervical inflammation / 中国综合临床

Objective To investigate the effect of small annular electrode assisted electrosurgical excision of cervical canal mucosa on cervical loop electrosurgical excision procedure ( LEEP ) in patients with cervical erosion and endocervicitis. Methods From March 2016 to March 2017,one hundred and twenty cases with cervical erosion treated in the Third People′s Hospital of Shenzhen were selected and were randomly divided into the control group and the observation group,with 60 cases in each group. The patients in the control group were treated with conical or LEEP while patients in the observation group were treated by putting the small ring electrode into the cervical canal under 0. 4 ～ 0. 6 cm longitudinal resection to treat cervical inflammatory lesions based on the treatment of the control group. The postoperative and postoperative recovery,postoperative efficacy and complications of the two groups were compared. Results There was no statistical significance between the observation group and the control group in the time of operation,the amount of bleeding during operation,and the time of vaginal drainage after operation ( P>0. 05 ) . The curative rate of the observation group and the control group were 75. 0％(45/60) and 51. 7％(31/60) at 1 month after operation respectively,and they were 95. 0％( 57/60) and 70. 0％ ( 42/60) at 2 months after operation. The difference was statistically significant ( P<0. 05) . The incidence of eversion of cervical columnar epithelium in the observation group and the control group were 5. 0％ ( 3/60) and 18. 3％ ( 11/60) at 1 month after the operation,and the difference was statistically significant (χ2=12. 4,P<0. 05) . The incidence of eversion of cervical columnar epithelium in the observation group and the control group were 3. 3％ ( 2/60) and 13. 3％ ( 8/60) at 2 months after the operation,and the difference was statistically significant (χ2=9. 51,P<0. 05) . No cervical laxity and stenosis occurred in both groups at 6 months after the operation. Conclusion The LEEP modified by small annular electrode can effectively improve the curative rate of cervical erosion in patients with endocervicitis, reduce the incidence of cervical columnar eversion,and does not prolong the operation time and does not increase the risk of bleeding or affect postoperative uterine function,which has good clinical value.

Clinical efficacy and safety observation of bevacizumab combined with docetaxel in treatment of advanced cervix cancer / 药物评价研究

Objective To explore the clinical efficacy and safety of bevacizumab combined with docetaxel in treatment of advanced cervix cancer.Methods Seventy-five patients with advanced cervix cancer accepted in our hospital from April 2011 to April 2016 were selected and divided into observation group with 43 cases and control group with 32 cases according to different treatment methods.Patients in control group were given docetaxel,and patients in observation group were combined with bevacizumab on the basis of control group.The clinical efficacy,adverse reactions,life quality and pharmacoeconomics of two groups were observed and compared.Results The total efficacy and clinical control rate of observation group were all higher than control group with statistically significance (P ＜ 0.05).The adverse reaction rate of two groups had no difference.Total efficacy of life quality improvement was 83.72％,which was obviously higher than control group 62.50％ with statistically significance (P ＜ 0.05).The average cost of observation group was (83 ± 10) thousands,of control group was (18± 6) thousands.The cost of observation group was obviously higher than control group with statistically significance (P ＜ 0.05).Conclusion Using bevacizumab combined with docetaxel in treatment of advanced cervix cancer has better effect clinical but costs much than docetaxel.We should set on treatment according to patients' own situation.

Influence of knowing about disease on hope level,anxiety and depression of patients with gastric cancer / 中国实用护理杂志

Objective To explore the influence of knowing about disease on hope level,anxiety and depression of patients with gastric cancer.Methods 120 gastric cancer patients were examined by Herth Hope Index,Hamilton Anxiety Scale(HAMA) and Hamilton Depression Scale(HAMD).Results Gastric cancer patients who did not know about their diseases accounted for 67.5％.Scores of hope level,anxiety and depression of patients were not obviously different between knowing and not knowing about disease groups.The relevant factors that affected the level of hope in gastric cancer patients were anxiety and family income.Conclusions The knowing or not knowing about disease are not the influencing factors that affected the hope level in gastric cancer patients as well as anxiety and depression.The relevant factors that affected the level of hope in gastric cancer patients are anxiety and family income.Patients can benefit from more factual information about the diagnosis.

Correlation between pharmacokinetics and pharmacodynamics of mycophenolic acid in liver transplant patients.

This study investigated the relationship between pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA) in liver transplant patients receiving mycophenolate mofetil (MMF). Total and free plasma MPA concentrations were determined by high-performance liquid chromatography before MMF dose and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing in 27 patients. The inhibitory capacity of serum MPA on proliferation of CEM cells was monitored at 0, 1, and 2 hours. The concentration of free MPA at 0, 1, and 2 hours (C(0h), C(1h), C(2h)) and the area under the concentration-time curve at 0 to 12 hours (AUC(0-12h)) of free MPA were significantly related to those of total MPA (P < .05). C(1h) and C(2h) of total and free MPA were conversely related with the rate of proliferation of CEM cells (P < .05). At 1 and 2 hours after an MMF dose, the percentage of CEM cell proliferation was below 40% in the majority of patients compared with the percentage before dosing. Thus, there was a significant relationship between total and free plasma MPA concentrations in liver transplant patients. After MMF dose, the inhibitory capacity of serum MPA on proliferation of CEM cells was enhanced significantly. This effect was related greatly to MPA concentrations.

Monitoring mycophenolic acid pharmacokinetic parameters in liver transplant recipients: prediction of occurrence of leukopenia.

Mycophenolate mofetil (MMF) is a very powerful immunosuppressive drug used in preventing acute rejection in liver transplantation. However, MMF has some serious side effects, including hematologic and gastrointestinal disorders. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in Chinese liver transplant recipients. Sixty-three adult liver transplant recipients receiving 1.0 g of MMF twice daily in combination with tacrolimus were prospectively included. The MPA pharmacokinetic profiles (blood sampling time points: before the dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after the dose) were monitored after transplantation. Every clinical event, including acute and MMF-related side effects, was monitored in all patients within 3 months. Two patients (3.2%) had an episode of acute rejection. Forty-two patients (66.7%) had 52 episodes of MMF-related side effects, including leukopenia, diarrhea, and infection. The 0-hour concentration (C(0h)), maximum (peak) concentration (C(max)), and area under the curve from 0 to 12 hours (AUC(0-12h)) in patients with side effects were significantly higher than those in patients without side effects (P < 0.05). The thresholds of side effects from receiver operating characteristic analysis were 2 mg/L (sensitivity, 52.4%; specificity, 90.5%) for C(0h), 10 mg/L (sensitivity, 45.2%; specificity, 85.7%) for C(max), and 40 mg h/L (sensitivity, 71.4%; specificity, 61.9%) for AUC(0-12h) (P < 0.05). Leukopenia was discriminated effectively in C(0h) and in C(max) (P < 0.05). These results demonstrate the close relationship between leukopenia and MPA pharmacokinetic parameters in the early period after liver transplantation. C(0h) and AUC(0-12h) of MPA could predict the subsequent occurrence of leukopenia. These values may be used in routine monitoring for MMF therapy.

Validation of limited sampling strategy for the estimation of mycophenolic acid exposure in Chinese adult liver transplant recipients.

Mycophenolate mofetil (MMF) is indicated as immunosuppressive therapy in liver transplantation. The abbreviated models for the estimation of mycophenolic acid (MPA) area under the concentration-time curve (AUC) have been established by limited sampling strategies (LSSs) in adult liver transplant recipients. In the current study, the performance of the abbreviated models to predict MPA exposure was validated in an independent group of patients. A total of 30 MPA pharmacokinetic profiles from 30 liver transplant recipients receiving MMF in combination with tacrolimus were used to compare 8 models' performance with a full 10 time-point MPA-AUC. Linear regression analysis and Bland-Altman analysis were used to compare the estimated MPA-AUC0-12h from each model against the measured MPA-AUC0-12h. A wide range of agreement was shown when estimated MPA-AUC0-12h was compared with measured MPA-AUC0-12h, and the range of coefficient of determination (r2) was from 0.479 to 0.936. The model based on MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h had the best ability to predict measured MPA-AUC0-12h, with the best coefficient of determination (r2=0.936), the excellent prediction bias (2.18%), the best prediction precision (5.11%), and the best prediction variation (2SD=+/-7.88 mg.h/L). However, the model based on MPA pharmacokinetic sampling time points C1h, C2h, and C4h was more suitable when concerned with clinical convenience, which had shorter sampling interval, an excellent coefficient of determination (r2=0.795), an excellent prediction bias (3.48%), an acceptable prediction precision (14.37%), and a good prediction variation (2SD=+/-13.23 mg.h/L). Measured MPA-AUC0-12h could be best predicted by using MPA pharmacokinetic parameters C1h, C2h, C6h, and C8h. The model based on MPA pharmacokinetic parameters C1h, C2h, and C4h was more feasible in clinical application.

Evaluation of the practicability of limited sampling strategies for the estimation of mycophenolic acid exposure in Chinese adult renal recipients.

The immunosuppressive potential of mycophenolic acid (MPA) correlates well with MPA exposure [area under the concentration-time curve (AUC)]. Monitoring MPA AUC is important and helpful for maintaining the efficacy of mycophenolate mofetil while minimizing its side effects, but full MPA AUC monitoring is laborious, cost prohibitive, and impractical. Limited sampling strategies have been proposed as an alternative method for estimating MPA exposure. The objective of this study was to evaluate the practicability of different limited sampling strategies for the estimation of MPA exposure. A total of 56 pharmacokinetic profiles from 53 adult renal recipients were used to evaluate the practicability of 10 published models. Standard correlation and linear regression analysis were used to compare the estimated MPA AUCs and corresponding full MPA AUCs, and the percentage of profiles for which prediction error fell within +/-20% was also used to assess the practicability of these models. Agreement between the estimated MPA AUCs and full MPA AUCs was further tested by Bland and Altman analysis. The model, based on four sampling time points, used the formula AUC = 12.61 + 0.37 x C0.5 + 0.49 x C1 + 3.22 x C4 + 8.17 x C10, was superior to all other evaluated models, with the highest coefficient of determination (r = 0.88), a low percentage prediction error (2.79%), and good agreement according to Bland and Altman analysis. Prediction errors of 87.5% (49/56) of profiles were within 20%, which was the highest of all the models. This algorithm can be reliably used for estimating MPA exposure in adult renal transplant patients treated with cyclosporine as concomitant immunosuppressant. Another model based on the formula AUC = 8.22 + 3.16 x C0 + 0.99 x C1 + 1.33 x C2 + 4.18 x C4 also has acceptable predictive performance, and it may also be practical, especially in outpatient settings, in view of its distribution of time points.

Limited sampling strategy for the estimation of mycophenolic acid area under the plasma concentration-time curve in adult patients undergoing liver transplant.

Mycophenolate mofetil (MMF), the oral prodrug of mycophenolic acid (MPA), is increasingly used in liver transplantation and plays a central role in the immunosuppressive regimen in liver transplantation. To study pharmacokinetic-pharmacodynamic relationships and therapeutic drug monitoring of MPA in the clinical setting, limited sampling strategies have been investigated for the estimation of MPA areas under the curves (AUCs). Thirty-eight adult patients undergoing liver transplant (31 males, seven females) receiving 1.0 g MMF twice daily and concomitant tacrolimus provided a total of 72 pharmacokinetic profiles. Multiple stepwise regression analysis was used to determine the algorithms for limited sampling strategies. Twenty-eight one-, two-, three-, and four-sampling estimation models were fitted (r = 0.288-0.964) to all the profiles using linear regression and were used to estimate MPA AUC0-12h comparing those estimates with the corresponding AUC0-12h values calculated with the linear trapezoidal rule, including all 10 timed MPA concentrations. The four-point estimates at C1h, C2h, C6h, and C8h resulted in the best correlation between estimated AUC and true AUC when using the formula AUC = 6.03 + 0.89C1h + 1.94C2h + 2.24C6h + 4.64 C8h (r = 0.911). Bland and Altman analysis revealed good agreement between estimated AUC and AUC from the full profile. This limited sampling strategy provides an effective approach for estimation of full MPA AUC0-12h in patients undergoing liver transplant receiving concomitant tacrolimus therapy.