Application of immunosuppressants in patients with autosomal dominant polycystic kidney disease after kidney transplantation / 南方医科大学学报

OBJECTIVE@#To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation.@*METHODS@#A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation.@*RESULTS@#The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% 96.0%, 94.1% 93.9%, and 90.6% 93.9%, respectively; > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% 96.0%, 90.8% 87.2%, and 79.0% 82.3%, respectively; > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms ( > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation ( < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group ( < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration ( < 0.05).@*CONCLUSIONS@#In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.

Meta-analysis of the Corre lation between CYP3A5 6986A＞G Gene Polymorphism and Blood Concentration of Cyclosporine A in Chinese Renal Transplantation Recipients / 中国药房

OBJECTIVE： To systematically evaluate the correlation between CYP3A5 6986A＞G gene polymorphism and blood concentration of Cyclosporine A （CsA） in Chinese renal transplant recipients. METHODS： Retrieved from Cochrane Library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， case-control or cohort studies about Chinese patients receiving CsA immunosuppressive therapy and blood concentration monitoring after kidney transplantation were collected. After literature screening and data extracting， the quality of literature was evaluated with Newcastle Ottawa scale， and Meta-analysis was performed by using Rev Man 5.3 software. RESULTS： Eight literatures with a total of 890 patients were involved in cohort study. Meta-analysis showed that the trough concentration after dosage correction （C0/D） of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*1/*3 genotype[MD＝－6.97，95％CI     （－13.18，－0.76），P＝0.03]. The subgroup analysis showed that the C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*1/*3 genotype when test time≤1 month after renal transplant [MD＝－8.50，95％CI（－12.57，－4.43），P＜0.000 1] and ＞1-＜6 months after renal transplant [MD＝－14.02，95％CI（－26.28， －1.76），P＝0.02]. C0/D of CsA in CYP3A5*1/*3 genotype was significantly lower than CYP3A5*3/*3 genotype [MD＝－6.04，95％CI（－8.99，－3.09），P＜0.000 1]. The subgroup analysis showed that C0/D of CsA in CYP3A5*1/*3 genotype was significantly lower than CYP3A5*3/*3 genotype when test time ≤1 month after renal transplant [MD＝－6.94，95％CI（－10.21， －3.68），P＜0.000 1]. C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*3/*3 genotype [MD＝－12.64，95％CI（－21.09，－4.20），P＝0.003]. The subgroup analysis showed that C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*3/*3 genotype when test time ≤1 month after renal transplant [MD＝－16.69，95％CI（－24.03，－9.36），P＜0.000 01] and ＞1-＜6 months after renal transplant [MD＝－16.78，95％CI（－28.63，－4.93），P＝0.006]. There was no statistical significance in CsA of peak concentration after dose correction between CYP3A5*1/*1 genotype and CYP3A5*1/*3 genotype， CYP3A5*1/*3 genotype and CYP3A5*3/*3 genotype， CYP3A5*1/*1 genotype and CYP3A5*3/*3 genotype. CONCLUSIONS： CYP3A5 6986A＞G gene polymorphism is associated with C0/D of CsA in Chinese renal transplantation recipients. The sequence of C0/D when test time ≤1 month after renal transplantation is as follows as CYP3A5*1/*1 genotype＜CYP3A5*1/*3 genotype＜CYP3A5*3/*3 genotype； during＞1-＜6 months after renal transplantation， C0/D of CsA in CYP3A5*1/*1 genotype＜CYP3A5*1/*3 genotype and CYP3A5*1/*1 genotype＜CYP3A5*3/*3 genotype.

Characteristics of BK polymavirus infection in kidney transplant recipients / 南方医科大学学报

OBJECTIVE@#To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs).@*METHODS@#We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×10 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×10 copy/mL (control group).@*RESULTS@#Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group ( < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (=0.351, < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min·1.73 m) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention.@*CONCLUSIONS@#Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.

Investigation and Analysis of the Application of Key Monitoring Varieties among Adjuvant Drugs in Medical Institutions of Yunnan Province / 中国药房

OBJECTIVE:To investigate the application of key monitoring varieties among adjuvant drugs in medical institu tions of Yunnan province,and to provide reference for the formulation of related policy and the promotion of clinical rational drug use.METHODS:The related data of key monitoring varieties in medical institutions of Yunnan province during Jan.1st-Mar.31st,2015 were investigated and analyzed statistically.RESULTS:The data with highest effective rate were reported by tertiary hospi tals,being 93.94％.Among top 10 drugs in the list of consumption sum,the number of key monitoring varieties was the highest in tertiary hospitals,being (5.50 ± 2.12) varieties averagely.The consumption sum of key monitoring varieties in tertiary hospitals took up the highest proportion in total consumption sum of hospitalization drug,being(31.94 ± 16.99)％ averagely;being(26.13 ± 11.93)％ and (22.14 ± 16.39)％ in second level hospitals and first level hospitals.Among top 10 drugs in the list of consumption sum,the consumption sum of key monitoring varieties in second level hospitals took up the highest proportion in total consumption sum of hospitalization key monitoring varieties,being (50.34 ± 26.87) ％ in average,up to 98.53 ％;being (39.13 ± 22.55) ％ and (27.38 ± 27.75)％ in tertiary hospitals and first level hospital.Among top 5 key monitoring types in the list of hospitalization con sumption sum,safflower yellow pigment and omeprazole were involved in hospitals at various levels.CONCLUSIONS:Adjuvant drug use are widespread in medical institutions of Yunnan province.Key monitoring varieties are given priority to TCM injection and proton pump inhibitors.It is necessary to take effective measures,formulate and implement the corresponding supervision sys tem so as to promote rational clinical drug use.

Investigation of the Construction Situation for Pharmacist Team in Medical and Health Institutions in Yun-nan Provence and Legislative Suggestions / 中国药房

OBJECTIVE:To provide data and reference for pharmacist legislation. METHODS:Questionnaire survey was de-signed investigate and analyze the staffing situation,education level,professional composition,age composition,professional titles composition,continuing education and wage of pharmacists who worked in medical and health institutions from 16 states (cities) in Yunnan province,and suggestions were put forward for relevant legislation. RESULTS:Totally 10 questionnaires were received from provincial medical and health institutions,and 16 from state (city) Health and Family Planning Commission,with effective recovery of 100%;data covered 1 561 medical and health institutions,involving 7 409 pharmacists. The numbers of pharmacy per-sonnel/hospital beds in tertiary hospitals,secondary hospitals and class-1 hospitals were 1∶15.49,1∶17.50,1∶20.68,numbers of pharmacy personnel/health professional and technical personnel in hospital accounted for 5.62%,6.18%,5.30%,respectively;most pharmacists in tertiary hospitals were mainly undergraduate degree(35.21%),doctor degree accounted for 0.15%,the high-est ratio of education was junior college degree in secondary hospitals(41.60%)and class-1 hospitals(57.51%);most pharmacists graduated in pharmacy in tertiary hospitals(94.14%),70.22% in secondary hospitals and only 10.50% in class-1 hospitals;phar-macy personnel mainly held the pharmacist professional titles in tertiary,secondary and class-1 hospitals (33.83%,37.89% and 63.55%),senior professional titles accounted for 5.88%,2.71% and 0.21%,respectively;only a few have learning experience and almost less than 6 months (9.17%,5.84% and 21.32%),and 80 pharmacists were certificated as clinical pharmacists in the whole province;generally,all wage was concentrated in 2 000-2 999 per month (27.72%,41.80% and 55.90%,respectively). CONCLUSIONS:Shortage of hospital pharmacists and lack of senior personnel are the main problems in Yunnan province,and wage is not high,especially in primary hospital,this situation is more obvious. The current situation of pharmacists in the hospital should be more taken into consideration during the legislative process in aspects of clearing and guaranteeing access qualifications, responsibilities,status,rights and interests,and pharmaceutical technology and service charges should be established.

Expression and relationship between hepaCAM protein and multidrug resistance protein in renal carcinoma / 国际肿瘤学杂志

Objective To investigate the expression and relationship between hepatocyte cell adhesion molecule (hepaCAM) protein and some multidrug resistance proteins in renal carcinoma tissue.Methods Expressions of hepaCAM,multidrug resistance associated protein (MRP),P-glycoprotein (P-gp),lung resistance protein (LRP),and topoisomerase Ⅱ (TOPO Ⅱ) protein were detected by immunohistochemistry in different areas of human renal cell carcinoma tissues and their relationships were analyzed.Results In the peripheral zone of renal tumor,hepaCAM,MRP,P-gp and LRP protein were showed positive expression.In the central region of the renal tumor,the expressions of hepaCAM,P-gp and LRP were negative or weakly positive,while the expressions of MRP and TOPO Ⅱ protein were positive.The expressions of MRP and TOPO Ⅱ protein in the central region of tumor were stronger than those in the peripheral zone of tunor (31.23 ±5.67 vs.23.89 ±4.56;45.66 ±2.34 vs.5.23 ±0.66),with statistically significant differences (t =-6.20,P =0.00;t =-100.16,P =0.00).While the expressions of other proteins (hepaCAM,P-gp and LRP) in the central region of tumor were weaker than those in the peripheral zone of tumor (3.21 ±1.12 vs.27.25±2.23;2.34±0.33 vs.51.23±3.45;4.22±1.78 vs.44.23 ± 1.45),with statistically significant differences (t =60.87,P =0.00;t =90.35,P =0.00;t =107.18,P =0.00).Correlation analysis showed that the expression of hepaCAM protein in the central region of renal carcinoma was related with the expression of MRP protein (r =0.94,P =0.01),but it was not related with the expressions of P-gp,LRP and TOPO Ⅱ protein (r=0.22,P=0.44;r=0.14,P=0.80;r=0.34,P=0.07).Conclusion The expression of hepaCAM protein in renal carcinoma may be related to tumor drug-resistance.

Histone deacetylase 6 and cytoplasmic linker protein 170 function together to regulate the motility of pancreatic cancer cells

Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes significantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 (HDAC6), a member of the class II HDAC family, is highly expressed at both protein and mRNA levels in human pancreatic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle progression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 (CLIP-170) and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.

End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability

Paclitaxel is a microtubule-targeting agent widely used for the treatment of many solid tumors. However, patients show variable sensitivity to this drug, and effective diagnostic tests predicting drug sensitivity remain to be investigated. Herein, we show that the expression of end-binding protein 1 (EB1), a regulator of microtubule dynamics involved in multiple cellular activities, in breast tumor tissues correlates with the pathological response of tumors to paclitaxel-based chemotherapy. In vitro cell proliferation assays reveal that EB1 stimulates paclitaxel sensitivity in breast cancer cell lines. Our data further demonstrate that EB1 increases the activity of paclitaxel to cause mitotic arrest and apoptosis in cancer cells. In addition, microtubule binding affinity analysis and polymerization/depolymerization assays show that EB1 enhances paclitaxel binding to microtubules and stimulates the ability of paclitaxel to promote microtubule assembly and stabilization. These findings thus reveal EB1 as a critical regulator of paclitaxel sensitivity and have important implications in breast cancer chemotherapy.

Systematic Review on Reduced Glutathione in the Treatment of Drug-induced Liver Disease / 中国药房

OBJECTIVE: To evaluate the efficacy of reduced glutathione in the treatment of drug-induced liver disease. METHODS: Literatures were retrieved from PubMed, Medline, EMBASE, Cochrane Library, CBM, VIP, CNKI databases by computer and from relevant Chinese medical journals by hand. Trial selection, quality evaluation and information extraction were performed according to including and excluding criteria. Meta-analysis was conducted using RevMan 5.0 software. RESULTS: The meta-analysis of 13 included RCTs showed that total effective rate, ALT and total bilirubin in trial group were significantly different from control group(P

Systematic Review on ~(131)I Combined with Antithyroid Drug in the Treatment of Hyperthyroidism / 中国药房

0.05).CONCLUSION:Results of study shows there is no significant difference between the therapy of 131I combined with ATD and 131I alone.

Meta-analysis on Itopride vs. Domperidone in the Treatment of Functional Dyspepsia / 中国药房

OBJECTIVE:To review the curative efficacy and safety of itopride vs. domperidone in the treatment of functional dyspepsia(FD). METHODS:Randomized controlled trails(RCTs)of itopride vs. domperidone in the treatment of FD were enrolled and retrieved from Cochrane Library,PubMed,EMBASE,SCI,CBM,CNKI,VIP and Wanfang Database. Other retrieval was carried out by hand. Methodological quality evaluation and meta-analysis of RCTs were carried out. RESULTS:Of total 18 RCTs enrolled,11 RCTs were graded B and 7 RCTs graded C. Itopride group were superior to domperidone group in respect of total response rate,the relief rate of nausea,abdominal distention,belching,vomiting,epigastric pain and sour regurgitation. There was no statistical significance. The incidence of ADR in itopride group was lower than in domperidone group. There was no statistical significance in difference between two groups. The relief rate of anorexia and early satiety in itopride group were superior to domperidone group. Statistical significance was noted in difference between two groups. CONCLUSION:Recent study shows itopride has better effect than domperidone on FD,which should be confirmed by high quality study.

Systematic Review on Xuezhikang in the Treatment of Type 2 Diabetes with Hyperlipoidemia / 中国药房

OBJECTIVE: To evaluate the efficacy of Xuezhikang in the treatment of type 2 diabetes with hyperlipoidemia. METHODS: Retrieved from Cochrane Library, PubMed, EMBASE, CBM, VIP and CNKI databases and related periodicals, included randomized controlled trails (RCTs) was evaluated in quality. Meta-analysis was conducted with RevMan 5.0 software. RESULTS: The meta-analysis of 6 included RCT showed that the improvement of TC, TG, LDL-C, HDL-C, FBS, 2 h-BS, HbA1c, UAE in trial group were different from control group. There was statistical significance in difference between 2 groups. CONCLUSION: Routine glycemic control combined with Xuezhikang has better effect than routine glycemic control in the treatment of type 2 diabetes with hyperlipoidemia. Because the number and quality of included study are not satisfactory, the study result should be confirmed by randomized double-blind controlled trial.