Progress on the protective effect of heme oxygenase-1 in viral infection / 药学学报

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

The screening and identification of internalized nanobody against EpCAM / 药学学报

Epithelial cell adhesion molecule (EpCAM) is a popular target for cancer therapy. In this research, 3 nanobodies with high specificity and endocytosis activity against EpCAM were developed, which provides a basis for the study of immunotoxin based on EpCAM. In our preliminary experiments, we have immunized a camel with EpCAM-Fc antigen and constructed a high-quality phage display library. Seventeen nanobodies with different complementarity determining region (CDR) 3 sequences have been screened after 3 rounds of biopanning by phage display technology. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. After purification, 7 nanobodies showed high cell binding activity by fluorescent activated cell sorting (FACS) identification. Furthermore, 3 nanobodies presented high endocytosis activity based on FACS and laser confocal microscopy, which also showed high affinity to EpCAM measured by ForteBio. According to this study, we aimed to provide a novel alternative approach to the EpCAM-targeted therapy and to provide guidance for the study of nanobody based immunotoxins for other targets.

Hyperbaric oxygen improves functional recovery of rats after spinal cord injury via activating stromal cell-derived factor-1/CXC chemokine receptor 4 axis and promoting brain-derived neurothrophic factor expression / 中华医学杂志(英文版)

BACKGROUND@#Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying the protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF).@*METHODS@#An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (n = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4; SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis.@*RESULTS@#HBO treatment recovered SCI-induced descent of BBB scores on POD 14, (1.25 ± 0.75 vs. 1.03 ± 0.66, P < 0.05), 21 (5.27 ± 0.89 vs. 2.56 ± 1.24, P < 0.05), and 28 (11.35 ± 0.56 vs. 4.23 ± 1.20, P < 0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89 ± 1.60 vs. 1.56 ± 0.98, P < 0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99 ± 1.60 vs.1.31 ± 0.98, P < 0.05; day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18 ± 1.60 vs. 0.80 ± 0.34, P < 0.05; day 21, SCI + HBO vs. SCI, 2.10 ± 1.01 vs.1.15 ± 0.03, P < 0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04 ± 0.41 vs. 2.75 ± 0.31, P < 0.05; day 14, SCI + HBO vs. SCI, 3.88 ± 1.59 vs. 1.11 ± 0.40, P < 0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO.@*CONCLUSIONS@#HBO might promote the recovery of neurologic function after SCI in rats via activating the SDF-1/CXCR4 axis and promoting BDNF expression.

Construction and screening of phage display library for TIM-3 nanobody / 药学学报

Immunotherapy is a new strategy for cancer treatment that has the potential to treat all types of cancer. T cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) is a key negative regulator of T cell activation. TIM-3 blockage using anti-TIM-3 monoclonal antibody therapy has a great appeal and special advantages. Nanobodies, derived from heavy chain fragment in camelid animals, are now proving clinical values in the development of antibody drugs. In this study, we have immunized camel with TIM-3 antigens and then constructed phage display library. Moreover, 29 nanobodies with different complementarity-determining regions sequences have been screened from the phage display library by phage display technology. In addition, we successfully constructed the cell line stably expressing TIM-3, and screened 10 TIM-3 nanobodies with high specificity and high affinity using flow cytometry. Our study will lay the foundation for the future screening and development of anti-TIM-3 whole humanized functional nanobody.

Role of Cervical Cerclage and Vaginal Progesterone in the Treatment of Cervical Incompetence with/without Preterm Birth History / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important health-care priority. The cervical incompetence is a well-known risk factor for PTB and its incidence is about 0.1-2.0%, while there is no ideal optimum treatment recommended currently. The cervical incompetence causes about 15% of habitual abortion in 16-28 weeks. This study aimed to evaluate the effectiveness and safety of cervical cerclage and vaginal progesterone in the treatment of cervical incompetence with/without PTB history.</p><p><b>METHODS</b>We retrospectively observed the pregnancy outcome of 198 patients diagnosed with cervical incompetence from January 2010 to October 2015 in Beijing Hospital. Among the 198 women involved, women who had at least one PTB before 32 weeks (including abortion in the second trimester attributed to the cervical competence) were assigned to the PTB history cohort, and others were assigned to the non-PTB history cohort. All women underwent cerclage placement (cervical cerclage group) or administrated with vaginal progesterone (vaginal progesterone group) until delivery. The outcomes of interest were the differences in gestational age at delivery, the rate of premature delivery, neonatal outcome, complications, and route of delivery between the two treatment groups.</p><p><b>RESULTS</b>Among the 198 patients with cervical incompetence, 116 patients in PTB history cohort and 80 patients in non-PTB history cohort were included in the final analysis. In the PTB history cohort, cervical cerclage group had significantly longer cervical length at 2 weeks after the start of treatment (23.1 ± 4.6 mm vs. 12.4 ± 9.1 mm, P = 0.002), higher proportion of delivery ≥37 weeks' gestation (63.4% vs. 33.3%, P = 0.008), bigger median birth weight (2860 g vs. 2250 g, P = 0.031), and lower proportion of neonates whose 1-min Apgar score <7 (5.9% vs. 33.3%, P = 0.005), compared with vaginal progesterone group. No significant differences were found in other outcome measures between the two treatment groups. In the non-PTB history cohort, there were no significant differences in the maternal outcomes between cervical cerclage and vaginal progesterone groups, such as median gestational age at delivery (37.4 weeks vs. 37.3 weeks, P = 0.346) and proportion of delivery ≥37 weeks' gestation (55.9% vs. 60.9%, P = 0.569). There were also no significant differences in the neonatal outcomes between the cervical cerclage and vaginal progesterone groups including the median birth weight (2750 g vs. 2810 g, P = 0.145), perinatal mortality (5.9% vs. 6.5%, P = 0.908), and 1-min Apgar scores (8.8% vs. 8.7%, P = 0.984).</p><p><b>CONCLUSIONS</b>Cervical cerclage showed more benefits in the maternal and neonatal outcomes than vaginal progesterone therapy for women with an asymptomatic short cervix and prior PTB history, while cervical cerclage and vaginal progesterone therapies showed similar effectiveness for women with an asymptomatic short cervix but without a history of PTB.</p>

The recent advances in the host targets of anti-influenza drugs / 药学学报

The challenge of the emergence of drug-resistant influenza strains, which is caused by wide spread utilization of direct-acting antivirals (DAAs), accelerates the research and exploration towards host targeted agents. In contrast to DAAs targeting viral replication components, host targeted agents, which regulate host factors and pathways linked to viral replication, can interfere the replication of influenza. Additionally, the innate immune system is activated by influenza during the early stage of infection, so manipulating the innate immune response may prevent the viral infection. However, the excessive inflammatory response induced at the late phase of influenza infection would lead to severe tissue injures. Thus, it is very important to explore drugs with anti-inflammatory actions to suppress these immune imbalances and tissue injures. Here we overview the current progresses about host targets related to anti-influenza drugs.

Recombinant human interferon alpha 2b broad-spectrum anti-respiratory viruses pharmacodynamics study in vitro / 药学学报

This study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. At the cellular level, the effect of the recombinant human interferon alpha 2b on influenza A virus was detected using real-time fluorescence quantitative RT-PCR. The effects of the recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus, respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic effect (CPE) method. In this study, the therapeutic index of recombinant human interferon alpha 2b anti-HPIV was 1476.63, the therapeutic index of recombinant human interferon alpha 2b anti-RSV was 141.37, the therapeutic index of recombinant human interferon alpha 2b anti-coronavirus was more than 2820.76, and the antiviral effect of recombinant human interferon alpha 2b was better than ribavirin (RBV). Recombinant human interferon alpha 2b has a stronger inhibitory effect on different influenza A virus RNA than drug control. The therapeutic index of recombinant human interferon alpha 2b anti-influenza B virus was 2.74, with modest effect. Recombinant human interferon alpha 2b in vitro has broad spectrum antiviral activities, low toxicity and high therapeutic index. Recombinant human interferon alpha 2b is expected to become the efficient medicine in clinical against respiratory viruses, as well as provide better services for prevention and treatment of respiratory viruses' infections.

Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Superficial urothelial carcinoma (SUC) of the bladder is a common urinary tract tumor in China. There is a high recurrence rate of this tumor even after surgery and intravesical instillation. Previous reports have described a suppression of the immune system in cancer patients. Dendritic cells (DCs) play a pivotal role in the induction of an effective antitumor immune response. The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients with bladder SUC.</p><p><b>METHODS</b>A total of 66 SUC patients and 38 healthy controls were enrolled in this study. All the patients had undergone transurethral resection (TUR) of their cancer and adjunctive IC after tumor removal. The patients were divided into a non-recurrence group (n = 40) and a recurrence group (n = 26) based on the presence or absence of tumor recurrence. Blood samples were taken preoperatively (PreOP), on postoperative days (POD) 1 and 7, and at postoperative month (POM) 3. Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets.</p><p><b>RESULTS</b>The preoperative percentages of myeloid dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls (P < 0.05). The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7, remaining higher than the preoperative values in POM 3 (P < 0.05). The percentages of mDCs, and CD80 and CD86 in the non-recurrence group on PreOP, POD 7, and POM 3 were higher than those in recurrence group.</p><p><b>CONCLUSIONS</b>Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function. Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.</p>

Appropriate use of immunosuppressants after renal transplantation / 中国医学科学院学报

Kidney transplantation has become an important method in treating advanced renal failure. Immunosuppressants play a key tool in this progress. It is important to understand the goal, mechanism, and adverse effects of immunosuppressive therapy, so as to appropriately use these drugs in post-transplantation patients on a customized basis.

Prevention and treatment of hypertension after renal transplantation / 中国医学科学院学报

Hypertension is a common complication after renal transplantation. Among post-transplantation patients died of cardiovascular diseases, about 41% have hypertension. Hypertension is an independent risk factor for kidney transplant failure. Post-transplantation hypertension can be caused by many factors, including the use of immunosuppressants. When the blood pressure exceeds 130/90 mmHg in a kidney transplant recipient, it is reasonable to provide active medical intervention. In summary, prevention and treatment of hypertension is important to prolong the survival of kidney transplant recipients.

Rapamycin instead of mycophenolate mofetil or azathioprine in treatment of post-renal transplantation urothelial carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Malignant tumor is the most common complication occurred in transplant recipients. It is widely recognized that immunosuppressive treatments increase the risk of cancer in transplant recipients. The efficacy and safety of rapamycin (RPM) in combination with low-dose calcineurin inhibitor (CNI) in treating 15 renal allograft recipients which developed urothelial carcinoma were observed.</p><p><b>METHODS</b>Immunosuppressive regimen in all recipients was altered with rapamycin to replace mycophenolate mofetil (MMF) or azathioprine (Aza). The initial loading dosage was 2 mg/d, and the next dosage was 1 mg/d. The dosage of rapamycin was carefully adjusted according to the blood drug level and concentration of the drug was maintained at 4 - 6 microg/L. In all the 15 patients, the calcineurin inhibitor was reduced down to one third of the original dosage after the rapamycin blood concentration became stable. Surgical treatment and intravesical instillation chemotherapy were carried out in all patients. Recurrence of the tumor was monitored throughout the study. Post-transplant renal function and side effects were also closely monitored.</p><p><b>RESULTS</b>Among the 15 patients, 9 had no tumor recurrence in 2 years, 2 had tumor recurrences twice, and 4 had once. There was no acute rejection observed during RPM treatment. Post-transplant renal function in 11 patients was improved, with a decreased creatinine level. Hyperlipoidemia and thrombocytopenia were the most frequent adverse events which responded well to corresponding treatments.</p><p><b>CONCLUSION</b>Among the renal allograft recipients with urothelial carcinoma, combination of rapamycin and low dose calcineurin inhibitor treatment is effective and safe.</p>

Aspergillus pneumonia in renal transplant recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Filamentous fungal infections are associated with a high morbidity and mortality in solid organ transplants. The present study aimed to investigate the aspergillus pneumonia in renal transplant recipients, and its diagnosis as well as treatment.</p><p><b>METHODS</b>Approximately 2000 cases of renal transplants were retrospectively studied and we focused on cases hospitalized during August 1, 2005 and February 1, 2007, as the study period. The clinical database and electronic records were analyzed. Recently published literature was reviewed.</p><p><b>RESULTS</b>There was more diabetes and hypertension in the infected group than in the non-infected group (86% vs 62% and 57% vs 39%, respectively). Eighty-six percent of recipients from the infected group had delayed graft function. Seven cases with aspergillus pneumonia were identified based on either fungal culture or radiology. Of the 7 cases, 4 died in a few days after diagnosis. Liposomal amphotericin B was used as a first-line therapy.</p><p><b>CONCLUSIONS</b>Incidences of fungal infection are increasing among renal transplant recipients. Early diagnosis and treatment are critical steps in curing aspergillosis.</p>

Prevalence and influential factors of erectile dysfunction in male renal transplant recipients: a multiple center survey / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Renal transplants can improve the quality of life for recipients, but the quality of their sexual life might not be improved. This study was conducted to research the prevalence of erectile dysfunction (ED) and the influential factors in male renal transplant recipients (RTRs).</p><p><b>METHODS</b>A cross-sectional survey was conducted in three renal transplantation centers. Structured questionnaires were administrated by trained interviewers to 824 male renal transplant patients, who had active sexual lives in the last 6 months.</p><p><b>RESULTS</b>Complaints of ED were reported by 75.5% of the 809 RTRs (age range 19 - 75 years, mean age (45 +/- 10) years), whose questionnaires were completed. Mild, moderate and severe ED were reported at 53.6%, 8.3% and 13.6%, respectively. The mean age and the graft duration were significantly higher in male RTRs with ED compared to potent graft recipients (P = 0.00 and 0.04, respectively). The prevalence of ED increased with the increase in age. It was 60.7%, 65.8%, 75.2%, 87.5% and 92.2% in patients with age below 30 years, 31 - 40 years, 41 - 50 years, 51 - 60 years and over 60 years, respectively (P = 0.000). Moreover, the severity of ED increased with aging. The percentage of moderate and severe cases of ED increased from 6.7% in patients below 40 years to 28.9% in those over 40 years (P = 0.000). The prevalence of ED in the RTR who had no occupation was higher than in those who were holding a position (P = 0.001). The prevalence of ED decreased with the increase in the education level. The prevalence of ED was 94.3%, 86.4%, 74.0% and 67.8% in men with elementary school or lower, middle school, high school, and college or higher degrees, respectively (P = 0.000). Patients, whose distal end of arteria iliaca interna was interrupted and underwent iterative transplantation, worried transplanted kidney function was impacted by sexual life, and received cyclosporine (CsA)-based immunosuppressive regimens, were more likely to have ED (P = 0.000, 0.001, 0.000, 0.000, respectively). After Logistic regression analysis, only five factors, age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life and CsA-based immunosuppressive regimens sustained their significance.</p><p><b>CONCLUSIONS</b>Renal transplant has varying effects on erectile function. ED is highly prevalent among RTRs and its influential factors are multiple. Age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life, CsA-based immunosuppressive regimens are the main influential factors of ED in male RTRs.</p>

Experimental study on effect of Bailing Cpsule on dendritic cells in mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>Comparing with the classic immuno-supressors, to probe in the in vitro effect of Cordyceps Sinensis (CS) on the differentiation, maturation and function of dentritic cells (DCs), and further to explore its mechanism.</p><p><b>METHODS</b>Mice myeloid DCs were cultured respectively with extraction of Bailing Capsule (CSE), a Chinese medical preparation made of CS, Rapamycin and Tacrolimus, and the effect of various drugs on phenotype of DCs was analyzed with flow cytometer. Then, using as the stimulator, the DCs cultured with different drugs were mixed and cultured with heterogenous lymphocytes for observing the stimulating capacity of DCs on cell proliferation.</p><p><b>RESULTS</b>CSE showed no in vitro effect on phenotype markers and co-stimulation molecules of DCs, the difference between CSE and Tacrolimus was insignificant, while Rapamycin could reduce the two parameters. CSE showed a marked suppressive effect on DCs in stimulating leucocyte proliferation in a dose-dependent manner.</p><p><b>CONCLUSION</b>CSE could affect the stimulating capacity of DCs on cell proliferation, which is probably by means of inhibiting the function of antigen presentating cells to block the presentation of extrinsic signal, and make the low immune response condition, thus to obtain the effect of immunosuppression.</p>

Clinical observation of qingxue granules in treating post-nephrotransplantation erythrocytosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic efficacy of Qingxue Granules (QX) in treating postnephrotransplant erythrocytosis (PNTE).</p><p><b>METHODS</b>Twenty patients were randomly divided into two groups according to the randomized table. QX was given to patients in the TCM treated group (QX group) and Enalapril given to patients in the Western medicine treated group (WM group), and the clinical efficacy in the two groups was observed. Results In the QX group, 3 patients got markedly effective, 2 effective, 2 improved, 1 ineffective, 1 dropped from the treatment, 1 absconded, with the total effective rate of 77.78%. The corresponding numbers in the WM group were 4, 2, 2, 1, 1 and 66.67%. There was no significant difference in comparison of the efficacies between the two groups (P > 0.05). There was no difference between the Intent-to-Treat population and Per-protocol Pouplation after statistical management of lost cases.</p><p><b>CONCLUSION</b>It has proved that QX has the same therapeutic effects as classic Western medical treatment in treating PNTE. The reliability and scientificity of QX was proved by Intent-to-Treat analysis.</p>

Population genetic analysis of Y-chromosomal single nucleotide polymorphism in six Chinese populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the genetic polymorphism of 15 single nucleotide polymorphism (SNP) loci on the nonrecombining portion of the Y chromosome in 6 populations in China.</p><p><b>METHODS</b>Allelic specific polymerase chain reaction and 2% agarose gel electrophoresis and 6% PAGE were used to analyze the genetic polymorphism of 343 unrelated males, representing 6 populations in China, including Fujian Hans, Sichuan Hans, Mongolian, Hezhen, Sibo and Hui from the South, Northeast and Northwest.</p><p><b>RESULTS</b>Thirty haplogroups were observed, and 3 of them (H15, H16, H18) were seen in all of the six populations. Although the heterozygosity levels of the Hezhen, Mongolian, Sibo populations are similar and those of the other 3 populations (Fujian Hans, Sichuan Hans, Hui) are similar, the pairwise differences among haplogroups are significant. Analysis of molecular variance (AMOVA) and principal component (PC) analysis of the haplogroup distributions suggested highly different allele diversity between group I including Hezhen, Mongolian, Sibo and group II including Hui, Fujian Hans, Sichuan Hans.</p><p><b>CONCLUSION</b>The above analyses show more significant variance components in Northeast/South populations and clearly reveal the geographic genetic relationship among the six populations in the Northeast/Northwest/South. These results confirm the complexity of the genetic structure of Chinese populations and make a significant contribution for constructing the contemporary human gene pool and tracing genetic dispersal trail from Chinese populations.</p>

Clinical analysis of urothelial carcinoma following renal transplantation / 中华泌尿外科杂志

Objective To analyze the clinical features of urothelial carcinoma in renal allograft re- cipients and to investigate its diagnosis and treatment.Methods A retrospective study was undertaken on 1293 renal allograft recipients in our center between 1998 and 2003.Of them ,21 cases(72.4% )had urothe- lial carcinoma(4 males and 17 females).All the cases had not had tumor before transplantation.In 17 cases the protopathy was chronic interstitial nephritis(CIN).The mean interval between tumorigenesis and trans- plantation was 26 months(range,6-62 months).Of the 21 cases,6 had bladder transitional cell carcinoma (TCC);6 had unilateral pelvic or ureter TCC;8 had unilateral pelvic or ureter and bladder TCC;1 had bilat- eral pelvic and ureter TCC.In 10 cases,the ipsilateral upper urinary tract of the graft was involved;and in 4 cases,the contralateral upper urinary tract was involved.Painless gross hematuria and iterative urinary tract infection were the cardinal symptoms.Surgical treatment was performed in 19 cases.Postoperatively,all the cases received immunosuppressants at one third reduction dose in combination with intravesical instillation chemotherapy.Results Two cases receiving palliative treatment died 5 and 8 months after diagnosis.The other 19 cases were followed for 2-5 years.Of them,13 cases had tumor recurrence.The recurrence sites were bladder and the contralateral upper urinary tract.All the cases had no acute rejection at reduced dose of immunosuppressants,and all had normal renal function except for 2 cases,who underwent removal of the graft and had dialysis again.Conclusions Renal allograft recipients whose protopathy is CIN and female recipients have the risk of urothelial carcinoma after renal transplantation.Urothelial carcinoma occurs more often in ipsilateral upper urinary tract of the graft than in contralateral upper urinary tract.Considering the high possibility of bilateral upper urinary tract involvement by TCC,prophylactic bilateral nephroureterectomy with bladder cuff excision should be considered in renal allograft recipients who have involvement of contra- lateral upper urinary tract of the graft.