Risk factors for urinary tract infection in kidney transplantation from brain death donor and its role in graft function. / è„‘æ­»äº¡å™¨å®˜æçŒ®è‚¾ç§»æ¤æœ¯åŽå‘ç”Ÿå°¿è·¯æ„ŸæŸ“çš„å±é™©å› ç´ åŠå ¶å¯¹ç§»æ¤è‚¾åŠŸèƒ½çš„å½±å“.

OBJECTIVES: Urinary tract infection (UTI) is the most common infection complication after kidney transplantation, and the reports of the incidence vary greatly among different centers. This study aims to explore the risk factors for UTI after kidney transplantation with the donation from brain death (DBD) and the impact on graft function, thus to provide theoretical basis for comprehensive prevention and treatment of UTI after kidney transplantation. METHODS: The clinical and laboratory data of DBD kidney transplantation from January 2017 to December 2018 in Xiangya Hospital, Central South University were collected and retrospectively analyzed. Patients were assigned into an UTI group and a non-UTI group. The base line characteristics, post-transplant complications, and graft function were compared between the 2 groups. Multivariate logistic regression was used to analyze the risk factors for UTI. RESULTS: A total of 212 DBD kidney transplant recipients were enrolled in this study. UTI occurred in 44 (20.75%) patients after transplantation. The female, the time of indwelling catheter, and postoperative urinary fistula were independent risk factors for UTI after DBD kidney transplantation. A total of 19 strains of gram-positive bacteria, 12 strains of gram-negative bacteria , and 10 strains of fungi were isolated from the urine of 44 UTI patients. The UTI after kidney transplantation significantly increased time of hospital stay (P<0.001) and raised the cost for antibiotics (P=0.004). The graft function was much worse in the UTI group compared with the non-UTI group (P<0.001) at 3 months after transplantation. Twenty (45.45%) patients recurred UTI within one year after transplantation. Non-hemodialysis before transplantation and perioperative combination of antibacterial and antifungal drugs were independent risk factors for recurrence of UTI. CONCLUSIONS: UTI after DBD kidney transplantation transplantation affects the renal function at 3 months and increases the patient's economic burden.

[Treatment of ureteral fistula and stricture following renal transplantation with Boari flap].

OBJECTIVE: To estimate the incidence rate of ureteral fistula and stricture after kidney transplantation, and to evaluate the effect of bladder flap (Boari flap) on ureteral complication of the transplanted kidney. 
 Methods: The clinical data and risk factors from 270 recipients of renal transplantation, who came from the Centre of Organ Transplantation, Xiangya Hospital, Central South University from January 2010 to January 2015, were retrospectively analyzed. The surgical management included Boari flap for ureteral reconstruction, neoureterocystostomy and endoscopic therapy with double-J (DJ) stent placement. Surgical proceeding and the effectiveness were evaluated.
 Results: The incidence rate of ureteral fistula following renal transplantation was 3.3%. The risk factors for ureteral fistula included elder donor age (P<0.05), delayed graft function (P<0.01), bladder spasm (P<0.05), and multiple renal arteries in allograft (P<0.01). Four cases were recovered after conservative treatment, and the other 5 cases were recovered after the treatment with Boari flap for ureteric reconstruction. The incidence rate of ureteral stricture was 4.4%. The risk factors for ureteral stricture included elder donor age (P<0.05), delayed graft function (P<0.05), cystospasm (P<0.05), ureteral fistula (P<0.01) and multiple renal arteries in allograft (P<0.01). Four cases underwent endoscopic therapy, 2 of them carried out percutaneous nephrostomy followed by antegrade DJ stent placement and the other 2 patients by retrograde DJ stent placement under ureteroscopy. Eight patients underwent surgery, 6 of them was treated by Boari flap for ureteral reconstruction and 2 patients were treated by neoureterocystostomy. All the patients recovered after surgical management.
 Conclusion: The ureteral complications after renal transplantation include ureteral fistula and stricture. Although the total incidence is low, the complications can result in adverse effects to the graft function and the life quality of the recipients. The risk factors for ureteral complication include elder donor age, delayed graft function, cystospasm, and multiple renal arteries in allograft. Ureteral fistula is the risk factor for ureteral fracture. Boari flap for ureterial reconstruction is an effective method in the treatment of the ureteral fistula and stricture.

miR-301a is a candidate oncogene that targets the homeobox gene Gax in human hepatocellular carcinoma.

BACKGROUND: MicroRNAs (miRNA) are a group of noncoding small RNAs that repress mRNA expression or induce mRNA degradation by binding to the 3'-untranslated regions of mRNAs. MiRNAs have been connected closely with the development of cancers such as hepatocellular carcinoma (HCC). However, the overexpression of microRNA-301a (miR-301a) has seldom been connected with tumorigenesis in HCC. AIMS: This study aims to characterize the function of upregulated miR-301a in HCC and show how the downstream growth arrest-specific homeobox (Gax) is negatively regulated by miR-301a. METHODS: The expression of miR-301a and Gax was detected using real-time PCR on HCC tissues and adjacent non-tumorous tissues. The luciferase reporter assay was used to assess Gax as a target of miR-301a. The nuclear factor κB (NF-κB) was measured by western blot after inhibiting miR-301a and enhancing Gax. The functions of miR-301a in vivo in HCC cells were measured by migration and invasion assays and flow cytometry. RESULTS: MiR-301a was significantly upregulated and Gax was downregulated in HCC samples compared with in the matching nontumoral tissues. Inhibiting miR-301a expression caused the upregulation of Gax and repressed NF-κB expression. We have shown that miR-301a plays an important role in increasing proliferation, migration and invasion and in inhibiting apoptosis of HCC cells. CONCLUSIONS: miR-301a is frequently upregulated in HCC and modulates NF-κB expression by negatively regulating Gax.

PDZRN4 suppresses tumorigenesis and androgen therapy-resistance in prostate cancer.

Background: PDZRN4 (PDZ domain-containing RING finger 4), a member of the LNX (ligand of numb protein-X) family that regulates the levels of NUMB, plays a critical role in suppressing the proliferation and invasion of hormone-related malignant tumours. There are few studies on the role of PDZRN4 in the pathogenesis of prostate cancer (PCa). We aimed to examine whether PDZRN4 regulates the growth and development of PCa. Methods: Cell transduction and Western blotting were used to establish and confirm PDZRN4 knock down in PC cells. Using the MTT, wound healing, transwell migration, and animal experiments, we explored the biological function of PDZRN4 knockdown (PDZRN4-kd) cells. Via PCR and immunohistochemistry, the mRNA and protein expression of PDZRN4 was examined in PC cells and tissues. Results: Hormone-dependent (LNCap) and hormone-independent (DU145, PC3, and C4-2) PC lines were transfected with lentivirus carrying PDZRN4 shRNA. The Western blotting results showed that the expression of PDZRN4 was stably downregulated in PDZRN4 knockdown (PDZRN4-kd) cells. The proliferation, invasion and migration of PDZRN4-kd cells were dramatically increased in vivo. To explore the expression of PDZRN4 in prostate cancer samples, we analysed TCGA data and found that PDZRN4 was negatively correlated with the development of PC. PDZRN4 levels were downregulated by androgen deprivation in hormone-sensitive cells. Moreover, PDZRN4 failed to induce proliferation in DU145 cells with androgen deprivation. Conclusions: PDZRN4 is a functional suppressor of prostate cancer growth and development and is a potential target of biochemical therapy in hormone-resistant PC.

Biological characteristics and epidermal growth factor receptor tyrosine kinase inhibitors efficacy of EGFR mutation and its subtypes in lung adenocarcinoma.

Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in lung adenocarcinoma (LAC). In this study, we extensively investigated the impact of patients' biological characteristics on EGFR mutation and the impact of EGFR mutation subtypes on targeted therapy of advanced LAC. We examined EGFR exons18to21status in169 LAC patients by direct sequencing to study the impact of patients' biological characteristics on the EGFR mutational spectrum. And then, 59 patients with advanced LAC harboring EGFR exon 19 deletions(del 19) or exon 21 point mutation(L858R) mutations received first-line treatment of gefitinib or erlotinib, the efficacy of treatment, and the progression-free survival (PFS) of these patients were recorded. The frequency of the EGFR mutation and its subtypes and the variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using all samples (n = 169). The EGFR mutation was significantly associated with well-differentiated tumor and excessive household cooking fumes(P < 0.05). The deletions in exon 19 were more frequently associated with well-differentiated tumor (P < 0.05). The overall frequency of the EGFR mutation was 49 %. Then the impact of EGFR mutation subtypes on targeted therapy were investigated by the retrospective analysis on 59 advanced LAC patients with del 19 or L858R mutations and treated first-line with erlotinib or gefitinib. The deletions in exon 19 got longer PFS (P < 0.05). But there were no differences in PFS between erlotinib therapy and gefitinib therapy. EGFR mutations were more frequently in high tumor differentiation and excessive household cooking fumes LAC. The del 19 mutation rate is relatively high with a high differentiation degree in advanced lung adenocarcinoma. The deletions in exon 19 may benefit more from first-line targeted therapy of advanced LAC compared with exon 21 point mutation L858R. There was no significant difference between the efficacy of gefitinib and erlotinib treatments associated with EGFR mutation and its subtypes.

Overexpression of MMSET is correlation with poor prognosis in hepatocellular carcinoma.

The multiple myeloma SET domain (MMSET) involved in the t(4;14)(p16;q32) chromosomal translocation encodes a histone lysine methyltransferase. High expression of MMSET is common translocation in multiple myeloma (MM) and is associated with the worst prognosis. Recent studies have shown that overexpression of MMSET is significant in other tumor types compared to their normal tissues. However, little is known about its role in hepatocellular carcinoma (HCC). In these study we investigate the expression of MMSET in HCC and to make correlations with clinicopathologic features. Twenty-eight pairs of HCC and adjacent non-tumor tissues, and eight normal liver tissues were collected for MMSET detection by western blotting and real time-PCR analysis. Immunohistochemistry was used to determine the expression of MMSET in HCC and adjacent non-tumor tissues from 103 patients. Overexpression of MMSET was significantly associated with Edmondson stage, vascular invasion. Moreover, Kaplan-Meier curves showed that MMSET upregulated was associated with shorter overall survival and disease-free survival in HCC patient. In conclusion, our study demonstrates for the first time that overexpression of MMSET is an independent prognostic factor and is correlated with poor survival in HCC patients.

Growth arrest-specific homeobox is associated with poor survival in patients with hepatocellular carcinoma.

Growth arrest-specific homeobox (GAX) codes for a transcription factor and plays a crucial role in many human cancers. Previous tumor studies have shown GAX may act as a suppressor of growth, invasion, and metastasis. However, little is known as to its role in hepatocellular carcinoma (HCC). Our aim was to investigate the expression of GAX in HCC and to make correlations with clinicopathologic features. Twenty-five pairs of HCC and adjacent non-tumor tissues, and six normal liver tissues were collected for GAX detection by Western blotting and real-time-PCR analysis. Immunohistochemistry was used to determine the expression of GAX in HCC and adjacent non-tumor tissues from 96 patients. Reduced expression of GAX was significantly associated with Edmondson stage, vascular invasion, and capsule invasion. Moreover, Kaplan-Meier curves showed that lower GAX expression was associated with shorter overall survival and disease-free survival in HCC patient. In conclusion, our study demonstrates for the first time that downregulated expression of GAX is an independent prognostic factor and is correlated with poor survival in HCC patients.