A double-J stent misguided by zebra guidewire into ileum: A case report and literature review.

The case is a 70-year-old man who underwent a left nephroureterectomy and cutaneous ureterostomy on the contralateral side for invasive bladder cancer had to be accepted replacement of the double-J stent because of stomal stenosis.When replacing the double-J stent, a severe complication that the double-J stent misguided into the ileum occurred. The patient underwent gastrointestinal motility drugs, and the double-J stent was excreted with the feces after 12 hours. Unfortunately，patient suffered a uretero-ileal fistula and died of septic shock finally.The diagnosis and management of Uretero-ileal fistula as an iatrogenic complication of zebra guidewire use is discussed.

Transurethral Incision of the Bladder Neck at Three Points with a Needle-Type Electrode for Bladder Neck Contracture.

Purpose: This study aims to evaluate the efficacy of transurethral incision of the bladder neck (TUIBN) at three points with a needle-type electrode for treatment of bladder neck contracture (BNC). Materials and Methods: Between January 2016 and April 2021, the bladder necks of 53 patients with BNC after surgery were incised by the needle-type electrode at the 5, 7, and 12 O'clock positions. Patient's preoperational characteristics, peri- and postsurgical outcomes, such as time of operation, postoperative bladder irrigation, and postoperative hospital stay, and data of the international prostate symptom score (IPSS), maximum flow rate (Qmax), and postvoid residual (PVR) were recorded 3 and 6 months after surgery. Results: All 53 cases of BNC were successfully treated in 35.00 (25.00, 45.00) min with 18.00 (14.00, 21.00) h for postoperative bladder irrigation with little intraoperative bleeding (less than 50 mL). The postoperative hospital stay ranged from 2 to 8 days, a mean of 3.50 (3.00, 5.00) days. No major intraoperative or postoperative complications were observed. All cases that underwent follow-up assessment at 3 and 6 months after the surgery showed significantly decreased IPSS and PVR and increased Qmax compared to preoperation ones (p ≤ 0.001). Of these 53 patients, there was no recurrence in severe BNC patients, but 5 of 53 (9.4%) BNC patients developed BNC again within 6 months and required repeated TUIBN. Thirty patients comprised five recurrent cases with a follow-up period of more than 1 year. Conclusions: TUIBN at three points provides a safe, effective, and reliable option in treating patients with BNC.

RIPK1 contributes to cisplatin-induced apoptosis of esophageal squamous cell carcinoma cells via activation of JNK pathway.

AIMS: Previous studies have uncovered the function of receptor-interacting protein kinase 1 (RIPK1) to mediate both cell survival and death. Moreover, RIPK1 modulates apoptosis and necroptosis depending on its activity, phosphorylation or ubiquitylation status. Many studies have explained the role or mechanism of RIPK1 in necroptosis. However, the role of RIPK1 has not been elucidated fully in human esophageal squamous cell carcinoma (ESCC) cells. MATERIALS AND METHODS: The protein and mRNA expression levels of RIPK1 in a panel of ESCC cell lines by Western blot and real-time quantitative reverse transcription PCR (qRT-PCR) were analyzed. MTS assay was used to examine cellular proliferation, flow cytometric analysis to detect apoptosis, mitochondrial membrane potential and reactive oxygen species production. ESCC cells with either inhibitor or overexpressed RIPK1were analyzed to determine cell proliferation, colony formation and apoptosis. Flow cytometry and western blotting assays were used to explore the underlying mechanism. KEY FINDINGS: In our study, RIPK1 expression was found to contribute significantly to cisplatin-induced apoptosis in the human ESCC cells. The reduced RIPK1 expression promoted cells proliferation and overexpressed RIPK1 facilitated cell apoptosis. Mechanistic investigations have revealed that the inhibition of proliferation for RIPK1 in ESCC cells was regulated via activation of c-Jun NH2-terminal kinase signaling. Additionally, damages were observed in the mitochondrial membrane, depletion of ATP and increased generation in reactive oxygen species. SIGNIFICANCE: Our findings verified the evidence that RIPK1 can promote cell death in ESCC cells, with potential implications for activating c-Jun NH2-terminal kinase pathway as a novel approach to the disease.

High Platelet Levels Attenuate the Efficacy of Platinum-Based Treatment in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: The correlation between platelet levels and clinical outcomes has received increasing attention, but it is not yet clear whether and how platelet levels affect the therapeutic response in non-small cell lung cancer (NSCLC). In the current study, we aimed to explore the role of platelet levels in responsive to platinum-based chemotherapy and investigated the underlying mechanism. METHODS: We evaluated the possibility of platelet level as a biomarker for response to platinum-based therapy in NSCLC by retrospective analysis of NSCLC patients. Cell proliferation was evaluated using cell counter and flow cytometry. Cell capillary-like structures of HPMEC were estimated with ECMatrix. The effect of platelets on A549, H1299, and HPMEC apoptosis was measured by flow cytometry. A A549-bearing NOD/ SCID mice model was employed to determine whether platelets could counteract cisplatin-induced apoptosis in vivo. In vivo cell proliferation and apoptosis were evaluated with Ki-67 antibody and TUNEL staining respectively. The angiogenesis of tumor was estimated by CD31 microvessel density. The protein levels of Akt, Bad and Bcl-2 were assessed by western blot. To further examine platelet-driven effects of the chemotherapeutic response, we used platelet depletion and platelet transfusion in A549-bearing NOD/SCID mice. RESULTS: Thrombocytosis at NSCLC diagnosis was associated with lower progression-free survival and median overall survival. Platelet levels before chemotherapy in the no response group were markedly higher than in the responsive group. Platelets rescued the inhibition of cell proliferation and angiogenesis and protected against cell apoptosis induced by cisplatin, platelets rescued cisplatin-induced apoptosis via the Akt/Bad/Bcl-2 signaling pathway under endoplasmic reticulum stress. Platelet transfusion decreased the therapeutic effect of cisplatin, while it was increased by platelet depletion. CONCLUSION: We confirmed an important anti-apoptosis mechanism mediated by platelets and found that platelets could counteract cisplatin-induced apoptosis. Reducing platelet levels or blocking platelet-based cytoprotection may represent new methods for improving the chemotherapeutic effect.

A comparative study on postoperative mortality prediction of SFLI scoring system and Child-Pugh classification in patients with hepatocellular carcinoma.

PURPOSE: In our previous study, we have established the clinical significance of the SFLI (scoring formula of liver injury), the purpose of this study was to compare the SFLI system and the Child-Pugh grading system in the prediction of postoperative mortality in patients with hepatocellular carcinoma (HCC). METHODS: 114 patients with HCC who underwent surgical treatment were enrolled. According to the requirement of the indicators for the Child-Pugh classification, various indices (including albumin [ALB], total bilirubin [TBIL], prothrombin time [PT], ascites, and hepatic encephalopathy) were considered in these patients before surgery, and then Child-Pugh grading was performed. Similarly, the serum biochemical markers including ALB, pre-albumin (PA), TBIL, serum creatining (SCR), international normalized ratio (INR), alanine transminase (ALT), aspartate transaminase (AST), γ-glutamyl transpeptidase (ggr;-GT), alkaline phosphatase (ALP), PT, activated partial thromboplastin time (APTT), and thrombine time (TT) were collected before surgery for SFLI analysis. The predicted postoperative mortality rates of these two scoring models and their diagnostic efficacy were analyzed and compared. RESULTS: According to the Child-Pugh grading system, in level A, B and C were 75, 35, and 4 cases respectively, and the corresponding mortality rates were 1.3% (1/75), 17.1% (6/35) and 75% (3/4). Meanwhile, according to the SLFI classification, the number of patients in the grade I, I+, II, and III were 36, 29, 28, and 21, respectively, and the corresponding mortality rates were 0, 0, 14.3% (4/28), and 28.6% (6/21), respectively. The patient mortality rate increased significantly with increasing grading (p<0.01). These two classification methods were further compared using ROC analysis, in which the area under the curve (AUC) for the Child-Pugh method was 10.2% with a 95% confidence interval (95% CI) 17-18, and the AUC of SFLI was 88.2% with a 95% CI 80-96. CONCLUSION: The SFLI scoring system is very useful in the assessment of liver function and postoperative mortality, and its grading standard is much better than the traditional Child-Pugh classification in many aspects.

Association between shortage of energy supply and nuclear gene mutations leading to carcinomatous transformation.

Anaerobic bacteria use glycolysis, an oxygen-independent metabolic pathway, whereas energy metabolism in the evolved eukaryotic cell is performed via oxidative phosphorylation, with all eukaryotic cell activities depending upon high energy consumption. However, in cancer cells evolving from eukaryotic cells, the energy metabolism switches from oxidative phosphorylation to glycolysis. The shortage of energy supply induces cancer cells to acquire specific characteristics. Base pair renewal is the most energy-consuming process in the cell, and shortage of energy supply may lead to errors in this process; the more prominent the shortage in energy supply, the more errors are likely to occur in base pair renewal, resulting in gene mutations and expression of cancer cell characteristics. Thus, shortage of energy supply is associated with carcinomatous transformation.

A retrospective study of paclitaxel combining nedaplatin chemotherapy for esophageal cancer.

The aim of this study was to evaluate the efficacy and tolerability of the combination of paclitaxel and nedaplatin in patients with advanced esophageal cancer. Patients (n = 310) with recurrent or metastatic esophageal squamous cell carcinoma, who had a maximum of one previous chemotherapy regimen, were enrolled in this study. All patients had bidimensionally measurable disease. Patients received 175 mg/m of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m in a 1 h infusion on day 1 every 3 weeks for up to 6 treatment cycles. The overall response rate was 47.7%, with complete and partial response rates of 6.1 and 41.7%, respectively. The median time to progression for all patients was 6.8 months (95% confidence interval, 6.2-7.4 months) and the 3-year disease-free survival probability was 3 (15.8%). The major toxicity observed was cumulative neutropenia, with 29% patients developing grade 4 toxicity. There was no treatment-related death. The most common nonhematologic toxicity encountered with this regimen was pain and cumulative peripheral neuropathy, with 26% patients experiencing grade 2 or 3 toxicity. The combination of paclitaxel and nedaplatin shows significant antitumor activity and a favorable toxicity profile in patients with metastatic carcinoma of esophageal cancer.

Net platelet angiogenic activity (NPAA) correlates with progression and prognosis of non-small cell lung cancer.

Circulating platelets are abundant sources of angiogensis molecules for the tumor vasculature affecting tumor growth and metastasis. The relationship between non-small cell lung cancer (NSCLC) and intra-platelet levels of VEGF, TSP-1 and net platelet angiogenic activity (NPAA) is unclear. The aim of this study was to better understand the role of these factors in the progression of NSCLC cancer and to assess its clinical significance. Platelet VEGF and TSP-1 and NPAA were measured preoperatively in 68 patients with NSCLC by ELISA or Capillary tube formation assay. VEGF, TSP-1 and NPAA distributions in cancer patients and healthy volunteers were compared using the Mann-Whitney U test. The Kaplan-Meier method, univariate and multivariate regression analysis was used to analyze the correlation between these factors and clinicopathological features, overall survival and disease-free survival. Mean intra-platelet TSP-1 level was slightly higher in patients than in healthy subjects (p = 0.092). Intra-platelet TSP-1 levels were significantly higher in patients with involvement greater than T2 or stage III, compared to other patients. Mean intra-platelet VEGF level was 40.8 pg/106 in patients compared to 21.9 ng/106 in healthy subjects (p = 0.041). Median value of NPAA in patients was significantly higher than that in healthy controls (p<0.001). Patients with high NPAA are more likely to exhibit aggressive clinical pathological features. NPAA greater than the median are associated with poor prognosis. The elevated NPAA have better correlation with tumor microvessel density (MVD) than platelet-derived VEGF. The areas under receiver operating curve (AUROC) of NPAA were higher than that of platelet derived VEGF in different groups. A multivariate analysis showed that NPAA are independent prognostic factors. These results indicated that NPAA may be a clinically useful indicator for diagnostic and prognostic evaluation in NSCLC patients.

Hypothesis of mitochondrial oncogenesis as the trigger of normal cells to cancer cells.

The Warburg Effect showed that energy metabolism of cancer cells was similar to prokaryotic cells, which were different from normal eucaryotic cells. The Endosymbiotic Theory offered a plausible explanation that the eucaryotic cells were evolved from prokaryotic cells, by which host cells (ancient prokaryotic cells) had ingested mitochondria (ancient aerobic bacteria), which depended on oxidative phosphorylation rather than glycolysis for generating energy. The alteration of energy metabolism might mean that the survival style of cancer cells were the re-evolution from eucaryotic cells to prokaryotic cells. But how this alteration happened was still unknown. This hypothesis tries to explain how mitochondria take part in the re-evolution from normal cell to cancer cell.

Expression of recombinant carcinoembryonic-antigen-human-ß-defensin-2 gene in colon cancer HCT116 cells.

The objective of this study was to construct a system driving high expression of human-ß-denfensin-2 (HBD-2) system in eukaryotic cell. To construct recombinant retrovirus expression vector, CEA signal peptide-HBD-2 (mature peptide sequence) was cloned in the retrovirus expression vector PLNCX2. The retroviral vector was transfected into PT67 cells by DOTAP; after screening and amplifying single clone cell by G418, the virus particles were collected and infected to eukaryotic, colon cancer HCT116 cells. Furthermore, the HCT116 cells were also screened by using G418 and the resistance clones were obtained. Finally, the expression of HBD-2 was detected by Western blotting, which suggested a high level of expression of HBD-2 in HCT116 cells. In conclusion, the results indicate that high level of HBD-2 expression was obtained in HCT116 cells which will help in effective commercial production and purification of HBD-2 protein.

Decreased tumstatin-mRNA is associated with poor outcome in patients with NSCLC.

Tumstatin is a candidate tumor suppressor that plays an important role in tumor growth and angiogenesis. The purpose of this study was to evaluate the correlation between tumstatin-mRNA expression and the clinicopathologic characteristics, tumor angiogenesis, outcome of patients with non-small cell lung cancer (NSCLC). Specimens from 68 patients with NSCLC were recruited in this study. Tumstatin-mRNA expression and protein level in tumor tissues were quantified respectively by quantitative RT-PCR and ELISA. Microvessel density (MVD) was determined by CD34 immunostaining. The correlation of tumstatin-mRNA expression levels with clinicopathologic variables, tumor angiogenesis, and prognosis was analyzed. Tumstatin-mRNA expression levels were decreased in tumor. Tumstatin-mRNA expression level was significantly correlated with its protein level in tumor (r = 0.562; P = 0.001). Tumstatin-mRNA expression levels in poorly differentiated tumor tissues were significantly lower than in well-differentiated tumor tissues (P < 0.004). Furthermore, tumor tumstatin-mRNA expression were also significantly related to tumor pathologic stage (P = 0.032) and MVD (r = -0.77, P < 0.0001). Overall survival (OS) and disease-free survival (DFS) analysis indicated that NSCLC patients with low tumstatin-mRNA expression had poorer OS and DFS than those with high expression (P = 0.015 and 0.037; respectively). Multivariable Cox regression analysis revealed that the tumstatin-mRNA expression could be an independent prognostic indicators in both DFS and OS. Tumstatin-mRNA expression levels are down-regulated in NSCLC tissues. Tumstatin-mRNA expression level correlates with prognosis, which suggests that tumstatin-mRNA is a new potential independent marker of favorable prognosis in NSCLC.

Association of TNF-α-308 and -238 polymorphisms with risk of cervical cancer: a meta-analysis.

Published data on the associations between tumor necrosis factor-alpha (TNF-α) promoter -308G>A and -238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model. 13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found no association between TNF-α-308G>A polymorphism and cervical cancer in overall population. In subgroup analysis, significantly elevated risks were found in Caucasian population (A vs. G: OR=1.43, 95% CI=1.00- 2.03; AA vs. GG: OR=2.09, 95% CI=1.34-3.25; Recessive model: OR=2.09, 95% CI=1.35-3.25) and African population (GA vs. GG: OR=1.53, 95% CI=1.02-2.30). An association of TNF-α-238G>A polymorphism with cervical cancer was found (A vs. G: OR=0.61, 95% CI=0.47-0.78; GA vs. GG: OR=0.59, 95% CI=0.45-0.77; Dominant model: OR=0.59, 95% CI=0.46-0.77). When stratified by ethnicity, similar association was observed in Caucasian population (A vs. G: OR=0.62, 95% CI=0.46-0.84; GA vs. GG: OR=0.59, 95% CI=0.43-0.82; Dominant model: OR=0.60, 95% CI=0.44-0.83). In summary, this meta-analysis suggests that TNF-α-238A allele significantly decreased the cervical cancer risk, and the TNF-α-308G>A polymorphism is associated with the susceptibility to cervical cancer in Caucasian and African population.

Development of an ELISA for quantification of tumstatin in serum samples and tissue extracts of patients with lung carcinoma.

BACKGROUND: Tumstatin, an angiogenesis inhibitor with anti-tumor activity in mice, is the bioactive NC1 domain of Col IVa3, the potential significance of tumstatin as an endogenous angiogenesis inhibitor in human is not yet completely understood. This study aimed to develop an enzyme-linked immunoassay (ELISA) for tumstatin to accurately measure its concentrations in biological samples. METHODS: Recombinant tumstatin as an immunogen was expressed by E.coli. The purified tumstatin was injected into mice for antibody generation. An ELISA was developed with the monoclonal antibodies. RESULTS: The detection limit of the ELISA was 1.4ng/ml, and the intra- and inter- assay CVs were within 10%. Recovery of tumstatin added to sera was 92.7-115%. Patients with metastases had serum tumstatin levels 50% lower than patients without metastases (P=0.039). Tumstatin levels in poorly differentiated tumor tissues were significantly lower than in nontumorous tissues and well-differentiated tumor tissues (P<0.001). CONCLUSIONS: The development of a highly sensitive and reliable ELISA method capable of quantifying tumstatin in human serum samples and tissue extracts is reported. This assay for tumstatin in biological samples may be helpful in evaluating the therapeutic and/or prognostic value of tumstatin in cancer patients.

[Treatment of acute myocardial infarction with autologous bone marrow stem cells mobilization combined with recombinant growth factor in rat].

OBJECTIVE: To observe the regeneration cardiomyocytes and neovascularization after mobilizing autologous bone marrow stem cells by granulocyte colony stimulating factor (G-CSF) alone or G-CSF combined with recombinant human growth hormone (rhGH) in Wistar rats with acute myocardial infarction (AMI). METHODS: AMI rat model was reproduced by liquid nitrogen cryoinjury. The rats were randomly divided into six groups: mobilization group (N group, n=8), sham operation group (SO group, n=6), myocardial infarction group (MI group, n=8), G-CSF group (G group, n=8), rhGH group (GH group, n=8) and G-CSF combined with rhGH group (GG group, n=8). White blood cell (WBC) count and mononuclear cells proportion (MNC%) in peripheral blood were determined with ABX blood cell analyzer to estimate bone marrow stem cells mobilization. Four weeks after intervention, the rats were sacrificed, their respective body and heart weight were obtained, and the hearts were harvested for hematoxylin and eosin (HE) and immunohistochemical examination. RESULTS: (1)Comparing with baseline values, after 6 days administration of G-CSF, the WBC and MNC% increased in N and G groups (both P<0.01); WBC increased (P<0.01) but no difference of MNC% in MI group (P>0.05); WBC and MNC% were significantly higher in G group than those in MI group (all P<0.05). (2)Body and heart weights in GH and GG groups were higher than those in SO, MI and G groups respectively (all P<0.05). The ratio of heart and body weight was higher in GC group than that in MI,G and SO groups (P<0.05). (3)There were no significant differences in infarct size among MI, G, GH, and GG groups (P>0.05). (4)The capillary densities were higher in G, GH and GG groups than those in MI and SO groups; the density in GG group was higher than that in G and GH groups (all P<0.01). (5)BrdU positively stained neonatal cells were observed in G, GH and GG groups. Of them some developed into the endothelial cells. BrdU and cTnI double positive stained cells were observed in G and GG groups, which implied these cells might have differentiated into cardiac myocyte like cells. CONCLUSION: (1)G-CSF can mobilize bone marrow stem cells into peripheral blood in normal and cardiac infarct rats. The mobilized stem cells may enter into the infarct zone and induce the regeneration of cardiac myocyte like cells and vascular endothelial cells. (2)rhGH may promote the regeneration of capillary in the zone of infarction, but does not induce regeneration of cardiac myocyte like cells. (3)The combination of G-CSF with rhGH might promote more capillary regeneration than either of them used alone.

[Review and analysis of revision of total hip replacement].

OBJECTIVE: To evaluate the clinical value of the revision of total hip replacement(THR), to analyse the reason of the revisions, and to discuss the main difficulties and measures to manage it. METHODS: From June 1998 to January 2002, 15 cases (15 hips) were revised on total hip replacement. The reasons for revision in the cases were as follows: failure of primary operative techenique, loosening and sinking of the components, displacement of the prosthesis, erosion of the acetabulum, as well as fracture of the femoral stem. The main difficulties of the revision were poor health condition of the patients; the remove of the prosthesis of the primary THR, especially the broken femoral stem and the cements; the loss of local bone. The measures to remove the broken femoral stem were described. RESULTS: All cases were followed up 2. 4 years on average: 2 patients died from heart disease and cerebrovascular disease respectively, while the good results were achieved in the others. No infection, dislocation, loosening, and other complications occurred. The good effects were related with following factors: mild degree of illness; no severe bone defect; most of the first femoral head replacement. CONCLUSION: The revision of THR is a more difficult operation, so that the special instrument and equipment and operative experience are required.

Characterization of excipient and tableting factors that influence folic acid dissolution, friability, and breaking strength of oil- and water-soluble multivitamin with minerals tablets.

The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a "super" disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production.