Reconstruction of fully shaped fingers using a free great toe nail flap combined with a second toe tissue flap.

To explore the clinical outcome of a free great toe nail flap (GTNF) combined with a second toe tissue flap (STTF) for fully shaped finger reconstruction (FSFR). From January 2013 to January 20, 2019, patients with finger defects underwent finger reconstruction using free GTNF combined with an STTF. All 20 fully shaped, reconstructed fingers survived without complications. The average follow-up time was 44.4 months (range 12-60 months). The reconstructed fingers had better function and appearance. The length of the fingers was close to normal, and the joint positions were normal. The fingers were able to extend -15° to -5° and flex 40° to 85°. The reconstructed fingers had no pain or numbness, and the function of the feet was restored well. The reconstruction of fully shaped fingers using GTNF combined with an STTF results in better function and appearance. This surgical method is worthy of promotion. This article introduces a new surgical method that is related to finger reconstruction. Finger defects bring psychological and functional regrets to patients and their families. Through this operation, the reconstructed finger is more perfect in appearance and function. I think this technology is very effective and worth promoting.

[Corrigendum] Knockdown of SNHG15 suppresses renal cell carcinoma proliferation and EMT by regulating the NF­κB signaling pathway.

Subsequently to the publication of the above article, the authors have realized that, on p. 390, the data selected for the siRNA­1 and siRNA­2 experiments for the ACHN and 786-O cell lines concerning both the invasion and the migration assays in Fig. 4B were selected inappropriately. Furthermore, after having inspected the published version of Fig. 5, the authors have realized that, for the immunofluorescence experiments shown in Fig. 5D, the first 'Merged' pictures for the first two columns of the ACHN cell line were accidentally published in the wrong order. The corrected versions of Figs. 4, and 5, including all the correct data for Figs. 4B and 5D, are shown on the next three pages. The authors confirm that these data continue to support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 53: 384­394, 2018; DOI: 10.3892/ijo.2018.4395].

Long non-coding RNA LINC02446 suppresses the proliferation and metastasis of bladder cancer cells by binding with EIF3G and regulating the mTOR signalling pathway.

Accumulating evidence has been obtained to understand the mechanisms of long non-coding RNAs (lncRNAs) in bladder cancer (BC). However, due to the recurrence and metastasis of BC, searching for lncRNAs that are related to prognosis and metastasis and exploring the pathogenesis of BC might provide new insights for the treatment of BC. In the present study, we used the TCGA and GEO databases and identified LINC02446 as associated with prognosis and differentially expressed in bladder cancer tissues and para-cancer tissues. Then, we found that LINC02446 could affect the proliferation, migration and invasion of BC cells. Additionally, we found that LINC02446 could bind to the EIF3G protein and regulate the protein stability of EIF3G and then inhibit the mTOR signalling pathway. In summary, all these findings show that LINC02446 might serve as a promising therapeutic target for BC intervention.

Exploring the five different genes associated with PKCα in bladder cancer based on gene expression microarray.

Much progress has been made in understanding the mechanism of bladder cancer (BC) progression. Protein kinase C-α (PKCα) is overexpressed in many kinds of cancers. Additionally, PKCα is considered an oncogene that regulates proliferation, invasion, migration, apoptosis and cell cycle in multiple cancers. However, the mechanism underlying how these cellular processes are regulated by PKCα remains unknown. In the present study, we used PKCα siRNA to knock down PKCα gene expression and found that down-regulation of PKCα could significantly inhibit cell proliferation, migration and invasion and induce apoptosis and G1/S cell cycle arrest in vitro. Overexpression of PKCα promotes tumour growth in vivo. We applied cDNA microarray technology to detect the differential gene expression in J82 cells with PKCα knockdown and found that five key genes (BIRC2, BIRC3, CDK4, TRAF1 and BMP4) were involved in proliferation and apoptosis according to GO analysis and pathway analyses. Correlation analysis revealed a moderate positive correlation between PKCα expression and the expression of five downstream genes. BIRC2 and BIRC3 inhibit apoptosis, whereas CDK4, TRAF1 and BMP4 promote proliferation. Essentially, all five of these target genes participated in proliferation, and apoptosis was regulated by PKCα via the NF-kB signalling pathway.

Phosphorylated MAPK14 Promotes the Proliferation and Migration of Bladder Cancer Cells by Maintaining RUNX2 Protein Abundance.

BACKGROUND: Mitogen-activated protein kinase 14 (MAPK14) acts as an integration point for multiple biochemical signal pathways. High expressions of MAPK14 have been found in a variety of tumors. Runt­related transcription factor 2 (RUNX2) is related to many tumors, especially in tumor invasion and metastasis. However, the mechanism of these two genes in bladder cancer remains unclear. METHODS: TCGA database and Western blot were used to analyze the mRNA and protein levels of the target gene in bladder cancer tissues and adjacent tissues. The proliferation ability of bladder cancer cells was tested by colony forming and EdU assay. The migration ability of cells was detected by transwell assay. Immunoprecipitation was utilized to detect protein-protein interaction. Cycloheximide chase assay was used to measure the half-life of RUNX2 protein. RESULTS: Phosphorylated mitogen-activated protein kinase 14 (P-MAPK14, Thr180/Tyr182) was highly expressed in bladder cancer tissues and bladder cancer cell lines. Accordingly, P-MAPK14 could be combined with RUNX2 and maintain its protein stability and promote the proliferation and migration of bladder cancer cells. In addition, the functional degradation caused by the downregulation of MAPK14 and P-MAPK14 could be partially compensated by the overexpression of RUNX2. CONCLUSION: These results suggest that P-MAPK14 might play an important role in the development of bladder cancer and in the regulation of RUNX2 protein expression. P-MAPK14 might become a potential target for the treatment of bladder cancer.

Knockdown of MAPK14 inhibits the proliferation and migration of clear cell renal cell carcinoma by downregulating the expression of CDC25B.

Mitogen-activated protein kinase 14 (MAPK14), which plays an important role in DNA damage and repair, is activated by various environmental stress and proinflammatory cytokines. It is highly active in a variety of tumors, acting as a tumor promoter or suppressor, but its role in clear cell renal cell carcinoma (ccRCC) has not been elucidated. Cell division cycle 25B (CDC25B) is involved in cell cycle regulation and is highly expressed in many malignant tumors. The transcription levels of MAPK14 and CDC25B in 72 pairs of ccRCC and adjacent healthy tissues from the cancer genome atlas database and the protein expression levels in 66 pairs of clinical samples were analyzed in this study. After MAPK14 was knocked down by small interfering RNA (siRNA), P-MAPK14 and CDC25B protein levels decreased. Subsequently, Western blot and co-immunoprecipitation demonstrated that P-MAPK14 could bind to CDC25B, potentially maintaining its stability. The proliferation and migration of ccRCC cell lines were suppressed by siRNA knockdown of MAPK14, however, that could be partially reversed by the overexpression of CDC25B. These results suggest that downregulation of MAPK14 and P-MAPK14 could inhibit the proliferation and migration of ccRCC by downregulating CDC25B.

Integrating bioavailability and soil aging in the derivation of DDT criteria for agricultural soils using crop species sensitivity distributions.

Although the agricultural use of dichlorodiphenyltrichloroethane (DDT) has been banned for decades in many countries around the world, the detection of DDT and its metabolites in soils is very common due to their persistence. DDTs (sum of DDT and its metabolites) in farmland soils can be absorbed by crops at different levels and accumulate in the edible parts of agricultural products, posing threats to the health of human being. However, no information on the species sensitivity distribution (SSD) of crops with regard to DDTs has been reported due to the lack of enough bioavailability data and models to normalize the bioavailability data from different sources. Based on the bioconcentration factors of 17 crop species in Chinese soils obtained from previous studies, the criteria of DDTs in soils was derived according to the quality standard of agricultural products using the SSD method. Corrections for water content and aging time were conducted to normalize the data from different sources. The risk values of agricultural products at different concentration levels of DDTs in soils were also evaluated. It was found that oil crops are able to take up more DDTs than non-oil crops, so the soil criteria were calculated separately for oil crops and non-oil crops, which were 0.083 mg/kg and 0.29 mg/kg, respectively. With the residual concentrations of DDTs in soils at the range of 0.01-0.5 mg/kg, 0-8% of the agricultural products exceeded the permissible limits for DDTs which were set in the National Food Safety Standard of China. The results also demonstrated the feasibility for applying SSDs to derive the soil criteria of DDTs in order to ensure the safety of agricultural products. This work will provide information for the risk assessment and the establishment of soil environmental quality standards to ensure safe agricultural production.

Knockdown of SNHG15 suppresses renal cell carcinoma proliferation and EMT by regulating the NF-κB signaling pathway.

Aberrant expression of long noncoding RNAs (lncRNAs) is associated with cancer tumorigenesis and progression. It has been suggested that lncRNAs may be potential clinical diagnostic and prognostic biomarkers, and therapeutic targets. In the present study, the expression levels of small nucleolar RNA host gene 15 (SNHG15) were significantly upregulated in renal cell carcinoma (RCC) tissues and cell lines compared with in adjacent tissues and a proximal tubule epithelial cell line, as determined by reverse transcription­quantitative polymerase chain reaction. Subsequently, knockdown of SNHG15 expression with small interfering RNA inhibited RCC proliferation, invasion and migration, was determined by western blotting and Transwell assays. Furthermore, the present study suggested that SNHG15 may be involved in the nuclear factor­κB signaling pathway, induce the epithelial­mesenchymal transition process, and promote RCC invasion and migration.

EIF2C, Dicer, and Drosha are up-regulated along tumor progression and associated with poor prognosis in bladder carcinoma.

EIF2C, Dicer, and Drosha are microRNA-regulating machinery components, which participate in microRNA intracellular process and transfer. Our research demonstrated the expression and clinical role of the microRNA-regulating machinery in bladder cancer. EIF2C1, EIF2C2, Dicer, and Drosha mRNA and protein levels were analyzed in 100 bladder carcinomas and 50 normal bladder tissues using quantitative polymerase chain reaction and Western blotting. EIF2C2, Dicer, and Drosha mRNAs and proteins were overexpressed in carcinoma compared with normal tissues, whereas EIF2C1 mRNA and protein were not obviously different. Moreover, immunohistochemistry was used to detect the expressions of EIF2C2, Dicer, and Drosha in 100 bladder carcinomas. There were higher EIF2C2, Dicer, and Drosha expressions in carcinomas than in the adjacent normal tissues, positive correlations being noted with clinical stage, histopathologic grade, and recurrence. Higher EIF2C2, Dicer, and Drosha expressions were related to shorter cancer-specific survival and shorter recurrence-free survival. Multivariate Cox analysis showed that EIF2C2 was an important risk factor in bladder cancer. In conclusion, EIF2C2, Dicer, and Drosha are more highly expressed in bladder carcinoma, promote the development of bladder cancer, and suggested a poor prognosis. Their clinical role in bladder carcinoma merits further research.

MicroRNA-141 is downregulated in human renal cell carcinoma and regulates cell survival by targeting CDC25B.

UNLABELLED: BACKGROUNDOBJECTIVE: MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids), approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC)25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. METHODS: Using miRNA target prediction software, we found that miR-141 could target the 3' untranslated region (3'UTR) sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR) in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site. RESULTS: miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells. CONCLUSION: For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development.

Knockdown of Cdc25B in renal cell carcinoma is associated with decreased malignant features.

Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.

Low microsomal epoxide hydrolase expression is associated with bladder carcinogenesis and recurrence.

Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

Overexpression of RIN1 associates with tumor grade and progression in patients of bladder urothelial carcinoma.

Ras and Rab interactor 1 (RIN1) is an effector of H-Ras, which plays an important role in the development and progression of carcinomas, but it has not been reported in bladder cancer. Hence, the association of RIN1 expression with prognosis of bladder urothelial carcinoma (UC) was examined. RIN1 mRNA and protein expression in 20 paired UCs and the adjacent normal tissues was detected by quantitative reverse transcription polymerase chain reaction and Western blot. The expression of RIN1 protein in 96 specimens of UCs and 22 specimens of adjacent normal bladder tissues were analyzed by immunohistochemistry. The overall survival (OS) was assessed by univariate and multivariate analysis. Moreover, the progression-free survival (PFS) and recurrence-free survival (RFS), classified by the clinicopathologic features with RIN1 expression, were assessed by multivariate analysis. RIN1 mRNA and protein level was higher in UCs than in the adjacent normal tissues (P < 0.01). Enhanced RIN1 immunoexpression was associated with high histologic grades (P = 0.046), cancer progression (P = 0.047) as well as Ki-67 expression (P = 0.023). Furthermore, the 5-year survival rate was 29% in the subgroup with high level of RIN1 expression, while it was 43% in the subgroup with normal level of RIN1 expression (P < 0.05). Importantly, RIN1 level was revealed as the significant independent prognostic factor for death (P = 0.023) and progression (P = 0.003), but a weak contribution for recurrence (P = 0.063). Collectively, RIN1 expression could be a potential prognostic predictor for UC patients.

The role of zinc transporter ZIP4 in prostate carcinoma.

OBJECTIVE: Normal prostate tissues have a unique function of accumulating high levels of zinc. This capability is lost during the early stage in the development of prostate malignancy. ZIP4 is an important zinc transporter. In this study, we explore the expression of ZIP4 in prostate carcinoma and invest the functional contributions of ZIP4 to cancer growth in vitro. METHODS: ZIP4 expression was detected in 14 prostate carcinoma and 20 BPH tissues by real-time RT-PCR and western blot. To invest the biological function of ZIP4 in prostate carcinoma cells, ZIP4 stable over-expression in cells was established in prostate carcinoma cell line DU145 (DU145-ZIP4) and ZIP4 short hairpin RNA(shRNA) expression in stable cells was also established in prostate carcinoma cell line 22RV1(22RV1-shRNA). The proliferation, migration, and invasion ability of the prostate carcinoma cells were detected. RESULTS: The expression of ZIP4 mRNA and protein are significantly down-regulated in prostate carcinoma tissues compared with that in BPH tissues. However, we found that there was no correlation between the ZIP4 expression and the pathologic grade of prostate carcinoma. In in vitro studies, over-expression of ZIP4 not only inhibits the proliferation but also inhibits the invasive ability of prostate carcinoma cell line DU145-ZIP4. At the same time, we found silencing of ZIP4 was associated with increased cell proliferation and invasion ability in 22RV1-shRNA cell line. However, both DU145-ZIP4 and 22RV1-shRNA cells showed a significant reduction on cell migration ability compared with the control. CONCLUSION: The results indicate that ZIP4 expression is down-regulated in prostate carcinoma and it may serve as a promising biomarker for prostate carcinoma. ZIP4 has an inhibitory effect on prostate carcinoma cell proliferation and invasion. It suggests that ZIP4 may be a tumor suppressor gene and down-regulation of ZIP4 may be a critical early event in the development of prostate carcinoma.

Urethral pull-through operation for the management of pelvic fracture urethral distraction defects.

OBJECTIVE: To present our institutional experience in the management of pelvic fracture urethral distraction defects with urethral pull-through operation. METHODS: Seventy-six patients (average age 34.5 years) with posterior urethral strictures caused by pelvic fracture urethral distraction defects underwent urethral pull-through operation at our department from July 1995 to September 2009. The estimated urethral stricture length was 2.0-3.5 cm (mean 2.5). Of these patients, 31 (41%) had undergone failed urethroplasty or urethrotomy after the initial management, and 5 (7%) had urethrorectal fistula. Urethral pull-through operation was performed 4-7 months (mean 4.9) after initial treatment or failed urethral reconstruction. The clinical outcome was considered a failure when any postoperative intervention was needed. RESULTS: Follow-up was 14-74 months (mean 42.5). The overall success rate was 89% (68/76). All treatment failures occurred within the first 6 months postoperatively. Failed repairs were successfully managed with internal urethrotomy in 1 patient, by urethral dilation in 6, and by another urethroplasty in 1. All patients were urinary-continent postoperatively. Of the potent patients, 2 (5%) became impotent after urethroplasty. There was no chordee, penile shortening, or urethral fistula recurrence. CONCLUSION: Urethral pull-through operation might be a less demanding and less time-consuming procedure. It does not increase the rate of impotence or incontinence and, with a high success rate, might serve as an alternative method for the management of pelvic fracture urethral distraction defects.

[Study on multiple aldosterone-producing adenomas].

OBJECTIVE: To investigate the experience on diagnosis and treatment of multiple adrenal aldosterone-producing adenomas (APA). METHODS: Eighteen cases of multiple adrenal APA were analyzed retrospectively, which were admitted from October 1992 to April 2006. RESULTS: Adrenalectomy was performed for 4 cases of unilateral synchronous multiple APA, which were discovered with three adenomas by 3D-CT; bilateral tumor resection was performed for 6 cases of bilateral synchronous multiple APA. There were 8 cases of bilateral metachronous multiple APA, including 2 cases of ipsilateral recurrent adrenal APA after adrenal tumor removal, which underwent tumor resection. Another 6 cases were contralateral APA following adrenalectomy due to adrenal APA, and underwent tumor resection. After operation, the adrenal function seemed to be normal, and no recurrence had been found on follow-up. CONCLUSIONS: Unilateral multiple synchronous APA require adrenalectomy. Tumor resection should be performed for bilateral or asynchronous APA, and it is very important to preserve healthy adrenal tissue as much as possible. 3D-CT has much value on diagnosis of small APA, unilateral multiple synchronous APA and ipsilateral recurrent adrenal APA.