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.

CLASP2 is involved in the EMT and early progression after transurethral resection of the bladder tumor.

BACKGROUND: Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localizes to the distal ends of microtubules and regulate microtubule dynamics. We speculated that it might be involved in the epithelial-mesenchymal transition (EMT) and progression of bladder cancer (BC). METHODS: Western blotting and RT-PCR were used to detect the changes at protein and mRNA levels in BC cell lines. Cell proliferation, clonogenic formation, wound healing and chamber invasion assay were used to investigate the abilities of cellular proliferation, migration and invasion. The data of BC patients treated with transurethral resection of the bladder tumor (TURBT) was collected and analyzed. The levels of mRNA of CLASP2 and EMT-related markers in tumor and urine samples were tested by RT-PCR. RESULTS: Expressions of CLASP2 varied in four BC cell lines. Manipulation of CLASP2 expression changed EMT-related markers. CLASP2 could promote proliferation, migration and invasion in BC cell lines. The combination (CLASP2 + E-cadherin mRNA in urine) could better discriminate the patients with or without 2-years progression compared with tumor grade after TURBT. CONCLUSION: CLASP2 is involved in the EMT and progression of bladder urothelial cancer. Simultaneous urine-based detection of CLASP2 and E-cadherin mRNA can efficiently discriminate patients with or without 2-years progression after TURBT.

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.

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

In this article which was published in Cell J, Vol 23, No 1, Spring 2021, on pages 51-60, the authors discovered that Figures 1B, 2D, 2F, 5B, and 5D some errors that occurred accidentally during figure organization in this article. The figures below have been corrected. The authors would like to apologies for any inconvenience caused.

Inhibition of miR-200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway.

OBJECTIVE: Patients with diabetes mellitus frequently have chronic wounds or diabetic ulcers as a result of impaired wound healing, which may lead to limb amputation. Human umbilical vein endothelial cell (HUVEC) dysfunction also delays wound healing. Here, we investigated the mechanism of miR-200b in HUVECs under high glucose conditions and the potential of miR-200b as a therapeutic target. MATERIALS AND METHODS: In this experimental study, HUVECs were cultured with 5 or 30 mM glucose for 48 hours. Cell proliferation was evaluated by CCK-8 assays. Cell mobility was tested by wound healing and Transwell assays. Angiogenesis was analyzed in vitro Matrigel tube formation assays. Luciferase reporter assays were used to test the binding of miR-200b with Notch1. RESULTS: miR-200b expression was induced by high glucose treatment of HUVECs (P<0.01), and it significantly repressed cell proliferation, migration, and tube formation (P<0.05). Notch1 was directly targeted and repressed by miR-200b at both the mRNA and protein levels. Inhibition of miR-200b restored Notch1 expression (P<0.05) and reactivated the Notch pathway. The effects of miR-200b inhibition in HUVECs could be reversed by treatment with a Notch pathway inhibitor (P<0.05), indicating that the miR-200b/Notch axis modulates the proliferation, migration, and tube formation ability of HUVECs. CONCLUSION: Inhibition of miR-200b activated the angiogenic ability of endothelial cells and promoted wound healing through reactivation of the Notch pathway in vitro. miR-200b could be a promising therapeutic target for treating HUVEC dysfunction.

Cancer-associated fibroblasts promote cisplatin resistance in bladder cancer cells by increasing IGF-1/ERß/Bcl-2 signalling.

While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERß in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERß expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERß signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERß/Bcl-2 signalling by either an shRNA targeting ERß or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERß/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance.

Significance of CLASP2 expression in prognosis for muscle-invasive bladder cancer patients: A propensity score-based analysis.

BACKGROUND: Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and is involved in various microtubule-dependent processes. We previously showed that CLASP2 is involved in the epithelial-to-mesenchymal transition of bladder urothelial cancer. This research aimed to explore the significance of CLASP2 expression as a prognostic marker for muscle-invasive bladder urothelial cancer (MIBC) patients after radical cystectomy-pelvic lymph node dissection (RC-PLND). METHODS: CLASP2 expression was analyzed in 76 benign bladder tissues and 160 MIBC tissues by tissue immunohistochemistry. Survival analysis and multiple regression analysis following propensity score matching were performed to investigate the correlation between high CLASP2 expression and MIBC patients' survival. RESULTS: CLASP2 expression was increased in MIBC patients, especially those with high-stage tumors or lymph node metastasis. In the follow-up of MIBC patients after propensity score matching, whether MIBC patients received adjuvant chemotherapy after RC-PLND, high CLASP2 expression was significantly associated with a poor prognosis. MIBC patients with low CLASP2 expression who received adjuvant chemotherapy tended to have an improved survival prognosis. CONCLUSION: CLASP2 expression is correlated with malignant progression of MIBC. High CLASP2 expression predicted a poor prognosis for MIBC patients after RC-PLND.

Laparoscopic Retroperitoneal Enucleation-Separation Surgery for Renal Angiomyolipoma: Perioperative and Oncologic Outcomes Based on a Randomized Controlled Trial.

OBJECTIVE: To report a novel technique of laparoscopic retroperitoneal enucleation-separation surgery for specifically located renal angiomyolipoma (RAML) treated in our institute. PATIENTS AND METHODS: We prospectively analyzed 40 patients who were randomized and received laparoscopic simple enucleation (Group 1) or enucleation-separation (Group 2) from January 2011 to February 2013. Patient characteristics, perioperative outcomes, renal function, and oncologic outcomes were compared between the groups. RESULTS: Average age, body mass index, sex distribution, tumor location and size, and operative time showed no significant difference between the two groups (p > 0.05). Average warm ischemia time in Group 1 was longer than that in Group 2 (25.3 minutes vs 17.6 minutes, p = 0.001). No complications except for one postoperative hemorrhage that occurred in Group 1 were observed. An improved early affected renal function recovery was observed in the Group 2 (percentage of glomerular filtration rate reduction for Group 1 vs Group 2, 24.3% vs 18.3%; p = 0.001). No local recurrences were found during the follow-up period. CONCLUSION: Laparoscopic simple enucleation and enucleation-separation technique are safe, efficient, and minimally invasive therapies for selected patients with RAMLs. In addition, the enucleation-separation appears to significantly minimize the warm ischemia injury and results in superior short-term renal function preservation, which could be a nephron-sparing alternative for the treatments of RAMLs.