Stem Cell Application for Stress Urinary Incontinence: From Bench to Bedside.

Stress urinary incontinence (SUI) is a common urinary system disease worldwide. Nowadays, medical therapy and surgery can control the symptoms and improve the life quality of patients. However, they might also bring about complications as the standard therapy fails to address the underlying problem of urethral sphincter dysfunction. Recent advances in cell technology have aroused interest in the use of autologous stem cell therapy to restore the ability of urinary control. The present study reviewed several types of stem cells for the treatment of SUI in the experimental and clinical stages.

Principle and progress of radical treatment for locally advanced esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is one of the most common malignant tumors in the digestive system in China and the world. Most patients are diagnosed as locally advanced or advanced stage. Concurrent chemoradiotherapy is the standard treatment for locally advanced esophageal squamous cell carcinoma. This study intends to summarize the evidence-based medical evidence of the treatment principle of locally advanced esophageal squamous cell carcinoma, the selection of radiotherapy dose, the outline of radiotherapy target and the selection of chemotherapy scheme. As a result, the effect of radiotherapy and chemotherapy is equivalent to that of surgery for the radical treatment of esophageal squamous cell carcinoma. In the era of immunization, it is recommended to use involved field irradiation. Fluorouracil plus cisplatin regimen is the standard chemotherapy regimen. FOLFOX regimen and paclitaxel plus fluorouracil regimen are optional concurrent chemotherapy regimens. The toxic and side effects of different chemotherapy regimens are different, which can be selected according to the actual situation of patients.

Up-regulation of circ_0000353 impedes the proliferation and metastasis of non-small cell lung cancer cells via adsorbing miR-411-5p and increasing forkhead box O1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common malignant tumor worldwide. This work focuses on investigating the role of circ_0000353 in NSCLC and its potential mechanism of action. METHODS: The expression levels of circ_0000353 and miR-411-5p in NSCLC and their matched normal lung tissues were detected by real-time PCR (RT-PCR). The correlation between the circ_0000353 expression and the clinicopathological parameters of NSCLC patients was also analyzed. CCK-8, BrdU and colony formation assays were adopted to detect the role of circ_0000353 in the proliferation of NSCLC cells. The metastasis of NSCLC cells was measured by Transwell assay. The dual-luciferase reporter gene assay was used to confirm the targeting relationship between circ_0000353 and miR-411-5p. The expression level of FOXO1 was detected by western blot. RESULTS: Circ_0000353 was significantly down-regulated in NSCLC tissues and cell lines, and the decreased expression was significantly linked to the increased clinical stage, larger tumor volume, and metastasis. The circ_0000353 over-expression restrained the proliferation, migration, and invasion of NSCLC cells in vitro. Additionally, up-regulation of miR-411-5p was observed in NSCLC tissues and cell lines, and luciferase assay and RT-PCR assay showed that circ_0000353 over-expression could target miR-411-5p and suppress its expression. Further studies confirmed that circ_0000353 and miR-411-5p modulated the FOXO1 expression. CONCLUSION: Circ_0000353 repressed the proliferation, migration, and invasion of NSCLC cells via inhibition of miR-411-5p and up-regulation of FOXO1.

Urinary trichloroacetic acid and high blood pressure: A cross-sectional study of general adults in Shijiazhuang, China.

Exposure to trichloroacetic acid (TCAA) and its parent chemicals potentially linked to cardiovascular disease. However, the association between TCAA and blood pressure (BP) has not been studied to date. The purpose of this study was to examine the potential association between urinary TCAA levels and BP in a Chinese population. We measured BP parameters (including systolic BP, diastolic BP and pulse pressure) and TCAA concentrations in the urine of 569 adults from a primary health care clinic in Shijiazhuang, China. Logistic and linear regressions were used to investigate the relationships between the urinary TCAA levels and BP parameters. To evaluate the robustness of the results, we conducted sensitivity analyses by re-analysing data after excluding urine samples with extreme specific creatinine values. We found that urine TCAA levels were positively associated with systolic BP and pulse pressure based on trend tests after adjusting for potential confounders (both p for trend < 0.05). Finally, only the association of TCAA with systolic BP remained significant in the sensitivity analyses (p < 0.05). Our results suggested that TCAA exposure was associated with increased BP in adults. Because urinary TCAA has been proposed as a valid biomarker of disinfection by-product (DBP) ingestion through disinfected drinking water, our results further suggest that exposure to drinking water DBPs may contribute to high BP in humans. Additional research is needed to confirm these findings and to evaluate opportunities for intervention.

Difference in failure patterns of pT3-4N0-3M0 esophageal cancer treated by surgery vs surgery plus radiotherapy.

BACKGROUND: There has been no study comparing the difference in the failure patterns between patients with or without postoperative radiotherapy (PORT) after esophagectomy for pT3-4N0-3M0 esophageal squamous cell carcinoma (ESCC). AIM: To investigate the difference in the failure patterns of stage pT3-4N0-3M0 ESCC patients with or without PORT. METHODS: Patients with stage pT3-4N0-3M0 ESCC, who underwent surgery with or without PORT, were enrolled in this study. The primary endpoint was to investigate the difference in the failure patterns between patients with or without PORT after esophagectomy. The secondary endpoint was to estimate whether patients with stage pT3-4 ESCC could achieve a disease-free survival (DFS) advantage after receiving adjuvant PORT. Statistical analyses were performed by the Kaplan-Meier method, Cox regression model, and Chi-squared test or Fisher's exact test. RESULTS: In total, 230 patients with stage pT3-4N0-3M0 ESCC were included in this study. Fifty-six patients who received PORT were screened from a prospective cohort (S + R arm). And 174 patients involving surgery alone were retrospectively selected from July 2006 to October 2014 (S arm). There were no significant differences in the clinical or pathological characteristics of patients between the two arms, except for tumor location (P = 0.031). The failure patterns between the two arms were significantly different (P < 0.001). Patients in the S arm had a significantly higher proportion of locoregional recurrence and a lower proportion of distant metastasis than those in the S + R arm (92.0% vs 35.7%, P < 0.001 and 19.0% vs 75.0%, P < 0.001, respectively). The difference in the median DFS between the two arms was statistically significant (12.7 vs 8 mo, P = 0.048). Univariate analysis and multivariate analysis both demonstrated that the number of lymph node metastases ≥ 3 (HR = 0.572, 95%CI: 0.430-0.762, P < 0.001) was an independent poor prognostic factor for DFS in patients with stage pT3-4N0-3M0 ESCC. CONCLUSION: PORT could improve DFS and local control of patients with stage pT3-4N0-3M0 ESCC. However, further studies need to be conducted to control hematogenous metastasis after PORT.

Diosgenin attenuates neuropathic pain in a rat model of chronic constriction injury.

Diosgenin is a steroidal saponin extract from numerous plants, including Solanum and Dioscorea species, and has been reported to possess neuroprotective activity. However, the role of diosgenin in neuropathic pain remains unclear. The present study examined the effects of diosgenin on allodynia and the levels of inflammatory mediators in rats following neuropathic pain evoked by chronic constriction injury (CCI). In addition, the underlying molecular mechanisms involved in diosgenin­induced suppression of neuropathic pain were examined. The results of the present study demonstrated diosgenin reversed CCI­decreased mechanical withdrawal threshold and thermal withdrawal latency. Furthermore, diosgenin inhibited CCI­induced upregulated levels of the pro­inflammatory cytokines tumor necrosis factor­α, interleukin (IL)­1ß and IL­2, and suppressed oxidative stress induced by CCI in the spinal cord. Furthermore, diosgenin significantly inhibited the expression of phosphorylated­p38 mitogen activated protein kinase (MAPK) and nuclear factor (NF)­κB in the spinal cord in CCI rats compared with sham­operated rats. In conclusion, the present study demonstrated that diosgenin attenuates neuropathic pain in CCI rats by inhibiting activation of the p38 MAPK and NF­κB signaling pathways. These results implicate diosgenin in the treatment of neuropathic pain, which merits further clinical investigation.

Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer.

BACKGROUND: Previous data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy. METHODS: Medical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ 2 test. RESULTS: A total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815). CONCLUSION: This retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.

Comparative study of different seeding methods based on a multilayer SIS scaffold: Which is the optimal procedure for urethral tissue engineering?

Seeding cells efficiently and uniformly onto three-dimensional scaffolds is key for engineering urological tissue with an ideal histological structure in vitro. Using an optimized seeding technology allows cells to cooperate positively with biomaterials, resulting in successful reconstructive surgery. In this study, we used four different types of seeding methods in a scaffold of small intestinal submucosa (SIS). The efficiency of the sandwich co-culture, layered co-culture, static-agitation seeding, and centrifugation seeding methods were compared. It was demonstrated that dynamic seeding methods, such as static-agitation and centrifugation seeding, had superior cell-matrix infiltration and mechanical properties. The seeding time could be reduced by 5-10 min using the centrifugation method. Furthermore, functional assessment of the barriers revealed that this function was better in the centrifugation seeding method than in any other method. Our study suggests that both the static-agitation and centrifugation methods are suitable for cell seeding on SIS. There is no significant change in surface area of SIS with different seeding methods. These methods reinforce the physiological and mechanical properties of biomaterials and allow for the future in vivo study of tissue-engineered urethral reconstruction. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1098-1108, 2016.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage III non-small cell lung cancer: a preliminary report.

OBJECTIVE: In recent years, the combination of cetuximab and chemoradiotherapy (CRT) has been used to treat stage III non-small cell lung cancer (NSCLC); however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT (CCRT) in Chinese patients with stage III NSCLC. METHODS: Eligibility criteria were Zubrod performance status (PS) 0-1, forced expiratory volume in 1 second (FEV1) ≥1.2 L and adequate organ function. Enrolled patients received weekly cetuximab (initial dose of 400 mg/m(2) on day 1 of week 1 and a maintenance dose of 250 mg/m(2) on week 2 to the end of CCRT) with cisplatin/vinorelbine (NP) chemotherapy (every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy (TRT) (60-66 Gy/2 Gy). The primary endpoints were toxicity and feasibility. All patients received positron emission tomography-computerized tomography (PET-CT) scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node-metastasis (TNM) stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. RESULTS: Seventeen patients were enrolled and 16 completed the full regime. The overall response rate (ORR) was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval (CI): 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% (95% CI, 60.6-96.9%) and 58.8% (95% CI, 60.6-77.8%), respectively. Three patients remain progression-free to date, and the median progression-free survival (PFS) was 13.5 months (95% CI, 6.8-20.2 months). No treatment-related death occurred; however, 76% of the patients experienced grade 3+ adverse events (AEs), including nausea/vomiting, intestinal obstruction, and esophagitis (<6%), while other AEs were mostly of hematological nature (71%). The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL (P=0.027), SUV-T (P=0.025), and PS (P=0.006) as potential survival predictors, with a hazard ratio (HR) of 3.4, 3.7, and 9.9, respectively. CONCLUSIONS: The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by (18)F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Serum neuron-specific enolase levels were associated with the prognosis of small cell lung cancer: a meta-analysis.

This study aims to evaluate the association of serum neuron-specific enolase (NSE) levels with the prognosis of small cell lung cancer (SCLC). Literature retrieval, trials selection and assessment, data collection, and statistical analysis were performed according to the Revman 5.0 guidelines. Literature-based searching was guided to gather data and either fixed-effect or random-effect model was used to pool the hazard ratio (HR) according to the test of heterogeneity. A total of 11 eligible studies that included 3,497 SCLC patients and 3,344 control subjects were analyzed. About 68.6 % of patients had high serum levels of NSE, according to the cutoff value defined by the authors. The HR of high levels of NSE for overall survival (OS) was 1.74 times that of low levels of NSE in SCLC patients (95 % CI, 1.14 to 2.65; P = 0.01). Patients with high levels of NSE appear to have a poorer OS compared with those with low levels of NSE.

Clinicopathological and prognostic significance of EGFR over-expression in esophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND/AIMS: To elucidate the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) over-expression in esophageal squamous cell carcinoma (ESCC). METHODOLOGY: A meta-analysis of previous studies was performed to assess the effects of EGFR over-expression on clinicopathological parameters and overall survival (OS) in patients with ESCC, using pooled odds ratio (OR) with its 95% confidence interval (CI) and pooled hazard ratio (HR) with its 95% CI, respectively. RESULTS: A total of nine studies including 802 patients were subjected to the final analysis. The overall results suggested that over-expression of EGFR was significantly correlated with, not only the lymph node status and tumour differentiation grade, with a pooled OR of 0.64 (95% CI: 0.46-0.89; Z=2.62; p=0.009) and 1.60 (95% CI: 1.09-2.37; Z=2.37; p=0.018), respectively, but also the poorer OS with a pooled HR of 1.60 (95% CI: 1.05-2.43; Z=2.19 p=0.028). CONCLUSIONS: This meta-analysis suggests that over-expression of EGFR might play an important role in the progression of ESCC, and it might be useful as a predictive biomarker in clinical practice, yet the predictive value of EGFR in ESCC still needs further confirmation by prospective trials.